Notable News – December 2018

Here we are on the cusp of another trip around the sun, and we have the opportunity to look forward to what the new year may bring. According to cancer.gov and cdc.gov, statistics found here and here, are encouraging when it comes to cancer survival rates. The number of cancer survivors in the United States is expected to reach 20.3 million by 2026. That’s good news for the 38.4 percent of men and women in the US that will receive a cancer diagnosis at some point in their lifetimes. Of course, surviving cancer can be costly. Expenditures for cancer care, which were $147.3 billion in 2017, are expected to increase in the coming years thanks to factors such as a population that is aging and new and costlier treatments which are implemented as standards of care. While cancer care is expensive, it seems to be effective. The overall cancer death rate has been steadily declining in the US since the 1990s. In fact, from 1991 to 2015, the overall cancer death rate fell 26 percent. According to cdc.gov, by 2020 the cancer death rates are expected to drop the most for prostate cancer, colorectal cancer, lung cancer, female breast cancer, oral cancers, cervical cancers, and melanoma. With the death rate falling and the survivor rate increasing it’s clear that, over the past several years, progress has been made to effectively prevent and treat the disease. Fortunately, it looks like 2019 will follow that trend.

There are two promising cancer treatment developments this month, reports medicalnewstoday.com. The first one helps prevent the spread of cancer after surgery. A spray-on gel being developed could help stop the recurrence and spread of cancer tumors after surgery when it is applied to the surgery site. The gel is full of drugs that activate the immune system to prevent the return of the cancer. Testing done on mice has been promising. It prevented the recurrence of cancer at the surgery site and prevented tumors from forming in other areas of the body. You can find more details about the promising gel here.

The second development is an exciting combination of medications that may prevent tumor growth. A couple of years ago, researchers in Switzerland figured out that by combining metformin, a drug used to treat diabetes, with syrosingopine, a blood pressure drug, they could prevent cancer tumors from growing. The combination of the two drugs kills the cancer cells by cutting off their energy supply. You can learn more about how this dynamic drug duo works together to sock it to cancer here.

There’s also good news regarding breast cancer this month, reports standard.co.uk. This is really good news because it gives hope to women with one of the most aggressive forms of breast cancer. There aren’t many treatment options for triple negative breast cancer, but targeted antibody therapies might change that. Triple negative breast cancer does not respond to hormone treatment so patients have to be treated with surgery, chemotherapy, and radiation. The targeted antibody therapy would activate the patient’s immune system to fight the tumor. More about this exciting and developing treatment can be found here.

Of course, the best news of all comes when the cancer is no longer detectable, and that’s exactly what happened for a Texas girl this month, reports abc7chicago.com. The 11 year old had a rare and inoperable brain tumor, and she went through weeks of radiation. The radiation can stabilize or shrink the tumor and is the only course of treatment, but there is no cure. Inexplicably, the girl’s scans revealed that the tumor was no longer visible. While doctors call this case extraordinary, they say the long-term prognosis has not changed, and the tumor will likely grow back. In the mean time, the family says they prayed for a miracle and got it. More about this remarkable story, and a video, can be found here.

As we ring in 2019, let’s hope for more encouraging research and remarkable stories, and a day when all cancers disappear.

Returning To Work During or After Cancer Treatment: Part 2

This is the second part of a three-part series which deals with common concerns on returning to work after a cancer diagnosis.

In Part 1 of this series, I shared some tips with you on how to prepare for your re-entry into the workplace. In this article we will look at practical ways to handle issues such as fatigue and concentration, managing your workload, and dealing with stress.

Let’s start with some tips on coping with fatigue as it’s probably the biggest challenge you will face, regardless of whether you are working during treatment or returning to work after treatment has ended.

Coping With Cancer-Related Fatigue

Cancer-related fatigue (CRF) is increasingly recognized as one of the most common and distressing side effects of cancer and its treatments. It has been estimated that from one quarter to nearly all cancer patients experience CRF during and after treatment.  Although things generally improves after therapy is completed, some level of fatigue may persist for months, or even years, following treatment.

Commenting on the impact of CRF on her own work, Kate Bowles, who was diagnosed with breast cancer in 2013, says, “The main advice I give is that chemo related fatigue is real and lasting. And also that your priorities change, often in very empowering ways. I am very calm in my job, because I really know now that it’s just a job.”

A lot of cancer patients don’t report fatigue to their doctors because they think that nothing can be done for it. In fact, there are things that can be done to alleviate the debilitating effects of CRF.  If left untreated, fatigue may lead to depression and profoundly diminish your quality of life, so it’s important that you speak to your doctor if fatigue is an issue for you. Before you can address CRF specifically, your doctor needs to determine if there are any underlying medical issues which may be contributing to your fatigue.

Making some adjustments to your everyday routines can also help you cope with CRF.

Here are three ways to do this.

1. Make deposits in your ‘energy bank’

You may find it helpful to think of your energy reserves as your ‘energy bank’. Whenever you do an activity you make a withdrawal. And when you rest you make a deposit. It’s important to balance withdrawals with deposits. If you keep doing too much whenever you feel like you have energy, you’ll run out completely and not have any reserves left for the things that are important.

2. Plan your day

Planning is key when you have fatigue. Write a ‘To Do’ list each evening so you can prioritize the things you need to do at work the next day.

3. Do some regular light exercise

Try to get out in the fresh air for a walk at lunchtime.  Although exercising may be the last thing you feel like doing when you’re tired, if you don’t exercise, you’re more likely to experience fatigue.

I also recommend you download a free app called Untire, which contains a program that will help you track and improve your energy levels. The app uses theories and techniques from scientifically proven cognitive behavior therapy, mindfulness-based cognitive therapy, positive psychology and physical exercise interventions.

Time Management 

Managing your time at work is all about learning to work smarter, not harder.  It’s not about packing more tasks into your day, but about streamlining how you go about your work and prioritizing key tasks.

Here are seven tips to develop better time management skills.

1. Track your time and eliminate the non-essential

First things first. If you’re going to manage your time better, you need to figure out where you spend your time. Use a tool like RescueTime to track your activities for a week. This will help you determine how much you can realistically accomplish in a day, identify the time of day when you are most productive, and uncover daily timesucks, such as reading emails (unsubscribe from those e-mail lists you no longer need).  When we can clearly identify our daily time sinks and remove them, we become more focused and productive.

2. Do the most important thing first

Mark Twain once said, “If it’s your job to eat a frog, it’s best to do it first thing in the morning. And if it’s your job to eat two frogs, it’s best to eat the biggest one first.” The point that Twain was making is that you should take care of your biggest and most-challenging tasks first thing in the morning.

Each day, identify the one or two tasks that are the most important to complete, and get started right away on them. If a task is too big to complete in one day, divide it into smaller tasks to be spread out over several days.  When you have accomplished a task, mark it off your list with a pen. This provides a psychological boost as it gives you visual confirmation that you are getting somewhere.

3. Batch related tasks

Batching refers to the process of using blocks of time for specific repetitive tasks. Different tasks demand different types of thinking, so save yourself time and mental energy by focusing on one type of task before moving on to the next.

4. Focus on one task at a time

Finding it hard to concentrate is a common effect of having had cancer. To combat this, focus on one task at a time instead of multi-tasking.  Research tells us it can take up to 30 minutes to return your attention to whatever you were doing before an interruption. Put your phone away, close your email applications and any unnecessary browser windows on your computer. Concentrate fully on the one task you need to complete.

5. Take regular breaks

Allow yourself down-time between tasks.  Break for lunch and take additional short breaks throughout the day. Maintain your energy reserves with nutritious snack breaks. Pack nuts, fresh fruits and veggies, hummus, or low-fat cheese to take to work with you.

6. Set time limits for tasks

Give yourself a certain time by which you will complete a task. For instance, reading and answering email can consume your whole day if you let it. Instead, set a limit of one hour a day for this task and stick to it. The easiest way to do this is to assign a solid block of time to this task rather than answering email on demand.

7. Let go of perfectionism

Stop trying to be perfect. When you’re a perfectionist, nothing will ever be good enough. That means you’ll stick with a task long past the deadline. You’ll say yes to too many things and take on too much in an effort to prove to yourself, and others, that nothing has changed since your cancer diagnosis.

Sometimes you need to realize that good enough is sufficient and when you reach that point, then simply stop. This is not an excuse to do a poor job, but it is intended to give you permission to do a good job and then leave it there. Don’t waste precious energy and time polishing and perfecting something past that point.

Managing Stress

It’s normal to feel some stress on returning to work, so it makes sense to plan ahead for how to deal with stressful situations. Here are some tips to help you.

1. Identify your body’s stress response

How we experience stress is individual to each of us. Learning to tune into what happens in your body when you perceive a stressful situation is the first step in understanding your own individual stress response. Does your jaw clench? Is your breath shallow? Are your muscles tense? When you become more aware of your physical response to stress, it will help regulate the tension when it does occur.

2. Slow down and pay attention to your breathing

When stress hits, everything speeds up. Our thoughts race, our heart pounds and our breathing increases. This can make it difficult to think rationally. Consciously slow down your breathing. When we are stressed we tend to breathe more shallowly.  When you feel stressed, practice taking some slow deep abdominal breaths.  Deep abdominal breathing slows the heart down, lowers blood pressure and helps us feel calmer.

3. Come back to your senses

One of the best ways to stop getting lost in your thoughts is to come to your senses and ground yourself in the present moment. A simple exercise is to notice five things around you. Practice this periodically throughout the day, especially at those times you find yourself getting caught up in your thoughts and feelings.

  • Look around and notice five things that you can see;
  • Listen carefully and notice five things that you can hear;
  • Notice five things that you can feel in contact with your body (for example, your feet upon the floor, your back against the chair);
  • Finally, do all of the above simultaneously.

4. Take Some Exercise

Physical activity is one of the simplest and most effective ways to reduce stress and anxiety – providing a natural outlet for your body when you are exposed to too much adrenaline.

Research has shown that there are many benefits to exercise. Not only does it help reduce the symptoms of fatigue, exercise encourages your body to release endorphins – often called ‘feel good hormones’. When released, endorphins can lift your mood and sense of well-being.

Go for a walk, head to the gym or find a lunch-time yoga class. Throughout the day take short breaks to stretch or do simple exercises at your desk.

Wrapping Up

Handling your re-entry to the workplace after a cancer diagnosis is all about organizing your time better, prioritizing your workload, establishing boundaries and becoming more comfortable with saying no to unreasonable demands.

Above all, it’s about making your health your top priority. Get adequate sleep, eat healthily, take some exercise and incorporate stress-management techniques into your daily routines.

I know from personal experience it isn’t always quite as straightforward as I have laid things out here. There will be many ups and downs. Deborah Bowman, a Professor of Medical Ethics, who was diagnosed with cancer in 2017, urges self-kindness and patience. “Don’t be afraid to say if it becomes unexpectedly (or expectedly!) difficult,” she says,  “be kind to yourself and allow others to be kind to you too. Accept it may be up and down rather than a straightforward trajectory. Celebrate your good moments and forgive yourself the harder moments.”


Next month in Part 3 of this Returning To Work series, we will take a look at the opportunities and challenges of finding a new job after cancer.  Until then, if you have any tips to share with readers about how you coped on returning to work, please share them in the comments below.

Myeloma Patient Cafe® November 2018 – Advocacy Opportunities for Myeloma Patients

Patient Advocate, Cindy Chmielewski (@MyelomaTeacher), leads this Myeloma Patient Café on advocacy opportunities for myeloma patients and care partners and the benefits of them.

5 Ways to Detect Cancer Before It’s Malignant

Cancer are diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. In 2018 statistics, Cancer appears to be the second leading cause of death worldwide. It is responsible for an estimated more than 9 million death in 2018. About 1 in 6 deaths globally are caused by Cancer. There are several main types of cancer. There are several causes of cancer, however the main cause of cancer is the change or mutation in the Deoxyribonucleic acid (DNA) of cells. There are some factors that would lead to cell mutation. Usually cancer cells are genetics and that means it is hereditary. Other factors also are, individual’s lifestyle, diet, smoking, environment such as exposure to radiations and exposure to viruses and other infections.

There are several types of cancer nowadays, however according to statistics the following are the most spread types of cancer:

  1. Lung (2.09 million cases)
  2. Breast (2.09 million cases)
  3. Colorectal (1.80 million cases)
  4. Prostate (1.28 million cases)
  5. Skin cancer (non-melanoma) (1.04 million cases)
  6. Stomach (1.03 million cases)

Symptoms of cancer may vary depending on the type of cancer an individual has. However common symptoms of cancer are already established according to studies. The C-A-U-T-I-O-N U-S mnemonics is already an established common symptom of cancer according to studies, viz:

C- Changes in bowel or bladder habits;

A- A sore that does not heal;

U- Unusual bleeding or discharge;

T- Thickening or lump in the breast or any other part of the body;

I- Indigestion or difficulty swallowing;

O- Obvious change in a wart or mole;

N- Nagging cough or hoarseness;

U- Unexplained Anemia;

S- Sudden Weight loss.

Like in most diseases early detection plays an important part in the prevention and intervention of diseases. The same concept is very important also in cancer. It would help a lot in determining what type of cancer a person has and correspondingly its proper management. Once cancer is early detected, it can be prevented from spreading more damages to the person’s body by providing adequate and proper remedies. In most cases, cancer can be detected by the individual upon experiencing the above stated signs and symptoms. Some cancer may cause severe pain in the affected body parts, while some may cause unusual bleedings, sores and other unusual tissue growth that are visible and palpable to the infected individuals. According to studies, there are established cancer self-assessment methods applicable to men and women. In women, the breast self-examination (BSE) is applicable. It can be done regularly by women usually upon taking a bath and every month for purposes of detecting any lump in the breast. In men, the Testicular self-examination (TSE) is applicable also with the same duration in women. However, there are some cancer cases that are asymptomatic. In these cases, diagnostic tests may be conducted by the proper medical experts.

The following are the 5 common ways or methods to detect cancer:

  1. Biopsy– In most cancer cases, biopsy is the main method to determine whether cells are cancerous. In this method, the doctor will get a tissue sample for examination to be used in diagnosing cancer. The method of getting tissue samples can be made possible either through an image-guided biopsy, ultrasound, x-ray, computed tomography scan (CT scan), fluoroscopy and magnetic resonance imaging (MRI). Depending on what method used by the doctor the purpose is just to aid in guiding a specific organ or body part where the tissue samples can be obtained.
  2. Barium Enema – In this method an enema is required to clear the colon for purposes taking images through X-Ray by a radiology technician. This is used to detect colon cancer.
  3. Ultrasound– This is a method of taking images on the body part where cancer is suspected. It uses high-frequency sound waves to create images of internal body organs. The sound waves hit the organs and bounce back to a device called a transducer. The transducer turns the sound waves into images that are shown on a computer. There are two individuals that will conduct this method. The first individual is the sonographer or the specialist that operates ultrasound machine. 12 hours before the test, the patient is required to be in a “nothing per orem” (NPO) status, which means that the patient will not be allowed to eat or to drink 12 hours prior to the test. However, 1 hour before the test the patient is required to drink a quart of water to keep full bladder. During the test, the patient is required to remove his clothes and any metal object and is required to lie down on the examination table. The sonographer will then apply the echo gel to the skin of the patient in order to block the air pockets for better imaging quality. The Sonographer will then press the transducer firmly against the gel and move it back and forth. After the images are taken, the second individual, the radiologist, which is a medical doctor will then interpret the images for purposes of diagnosing cancer.
  1. Bone Scan– This method uses a small amount of radiation to detect cancer cells that start to propagate in the bones and bone tissues.
  2. Endoscopy– This method uses a thin scope that has camera on its tip connected to the monitor in order to determine any lumps or unusual tissue growths in the patient’s Gastro-intestinal tract.

In most cancer cases globally, early detection is the key to prevent extensive damages that are caused by cancer cell proliferation. It is also very important for proper cancer management.

All I Want For Christmas Is Customer Service at My Doctor’s Office

I have this crazy dream. It’s about how, when I make an appointment to see my doctor – my primary care physician, my radiologist, my orthopedist, my whatever-ologist – the process is easy, honors my time as much as it does my doctor’s, and winds up running smoothly for both sides of the transaction.

The dream starts this way: I realize it’s time for an initial or follow-up visit to any of my doctors. I open up my browser, point it to my doctor’s website, and log in to the secure patient portal. The one where I can see all my prescriptions, my personal health record, make an appointment (using the handy calendar function), request a prescription refill, ask the nurse or doctor a question via email, or download a PDF of my health record.

In my dream, using the handy scheduling function in the portal, I select a date and time for my appointment. The portal auto-populates that date and time with my name and insurance/contact info, since I logged in and it knows who I am. The system asks me if any information has changed. I click “no”. If I click “yes,” the next screen asks me to make the changes, and “submit”.

I select the reason for my visit from the list of appointment types. I enter any information I need to related to this appointment request (i.e. “Doc, I have this pain…”). Then I click “submit” and the system sends me a confirmation email or text (I picked which one I prefer when I set up my profile on the portal). It also schedules me for a blood draw in the week prior to the appointment, sending me a confirmation for a walk-in at the lab.

The scene in my dream shifts to the day of my doctor’s appointment. I’m scheduled to be seen at 11:00am. I get a text at 10:00am – or an email, whichever I selected when setting up my portal profile – saying that the doctor’s running about 30 minutes behind. I can either come in at 11:30am, or select one of the alternate appointment times in the text/email and be re-scheduled.

I select 11:30am, and I arrive a few minutes before that time. Signing in involves scanning a key tag, or a bar code on a mobile app – just like the one you use at your favorite supermarket – which lets everyone in the practice, from the receptionist to the doctor, know that I’m there, and on time.

If the admin staff needs to talk to me for any reason, they’ll see me on their screen (usually because, in the day-before review, they checked the “confirm insurance details” or “update pharmacy info” or “collect co-pay” radio button) and invite me to have a private conversation. By using my first name only. No sign-in sheet (potential HIPAA violation) or yodeling my full name across a crowded waiting room (definite HIPAA violation).

By the way, in my dream the co-pay is collected by the system without having to get me or the staff involved. I’ve given the practice my credit/debit card number, and signed a consent form to allow automatic collection of my payment when I scan in for my appointment at the office.

I take a seat in the waiting room…for about 5 minutes. I’m called – first name only – by the nurse, who takes me back to an exam room. I scan in again in the room, and s/he checks my blood pressure, temperature, and heart rate using equipment tied into the practice’s IT network. Since I scanned in, the readings are loaded into my record instantly.

S/he and I chat for a minute or two, and then I’m left alone to disrobe. The doctor arrives minutes later, and proceeds with my exam. S/he enters information on a tablet, but spends most of the time talking to me about how I’m feeling lately, the results from my blood work, what my exercise program is these days, how about those Giants/Redskins/Bears/whoever, and if I’ve had any meds side-effects that I haven’t mentioned.

The doc tells me that my blood work shows everything’s A-OK, all my numbers look good. I’m up a few pounds, time to hit the gym a little harder to stop expanding midriff syndrome in its tracks. (It’s a dream, but it could become a nightmare.)

Face time. Real face time. Only about 10 minutes, yet I feel like I’ve been listened to, and engaged with, by my doctor. I feel like I’m recognized as a human participating in my healthcare, not a meat-puppet on a conveyor belt.

OK, I’m awake now. In a world where all of the technology tools to turn my dream into reality exist…but aren’t being used in any consistent way. Why not? Usually, I hear “they’re too expensive” or, my personal fave, “my staff doesn’t like technology.”

Guys, it’s the 21st century. It’s time for some technology-enabled user interface/user experience – called UI/UX in the design business – across the entire medical industrial complex. All of the technology I’ve dreamed out loud above exists, but it’s not in wide use across all medical providers. And EHR systems still don’t talk to each other, so even if one of my doctors has all of the tech-enabled features I’ve outlined working in their system, the data in their system can’t show up in another of my doctor’s systems … even if they’re part of the same healthcare provider system, on the same EHR.

Time to storm the castle, with people – the ones called “patients” – demanding actual customer service from the healthcare delivery system? I think so. Who’s with me?

Measuring My Myeloma With MRD Testing: What Is My Disease State?

Minimal residual disease (MRD) testing is a big topic of interest for many myeloma patients and care partners. What exactly is the role of MRD testing in myeloma, and is it worthwhile?

Downloadable Guide

Watch as Cherie Rineker, a myeloma patient, Dr. Elisabet Manasanch, an oncologist at MD Anderson Cancer Center and Tiffany Richards, an advanced practice nurse, discuss how myeloma is being measured to accurately define myeloma disease states.


Transcript:

Andrew Schorr:
Hello, and greetings from Southern California. I’m Andrew Schorr with Patient Power. Welcome to this Patient Empowerment network program. This should be very helpful over the next 90 minutes for all of you living with multiple myeloma. And some people, thank God, now have been living a long time. And we’re going to be discussing measuring my myeloma with MRD testing, what is my disease state. So, testing has come a long way, and we’re going to hear the latest.

Okay. Are you ready to go? All right. Now, let’s go to Houston, Texas. We have a lot of people to meet. And one of them is a physician who is a specialist in multiple myeloma. She is at the MD Anderson Cancer Center in Houston. And that’s Dr. Elisabet Manasanch. So, Dr. Manasanch, thank you so much for being with us. She’s going to pop herself on there. And thank you so much for being with us. And we’re going to learn a lot more about myeloma testing, as we go. Also, I want to have someone else join us from MD Anderson. She’s been on our programs before. She’s a nurse practitioner specializing in multiple myeloma. And that is Tiffany Richards. Tiffany, welcome to our program. Hi, Tiffany.

Tiffany Richards:
Hi.

Andrew Schorr:
Okay. And then, of course, on every program, we always have a patient. And some of you in the myeloma community have been following Cherie Rineker from Houston, who has been living with myeloma since 2012. Not too long ago, nine months ago, had CAR T-cell therapy. But she’s been through so many treatments, and she’s in Houston as well. Cherie, welcome to our program. Cherie is going to pop herself—hi, Cherie, welcome back.

Cherie Rineker:
Hi, Andrew. It’s great being with you again.

Andrew Schorr:
Okay. So, let’s hear a little bit of Cherie’s story because, for any patient going through, you want to know how are you doing. And then, we’re going to learn from the doctor and from Tiffany more about MRD testing or testing in general. And then, we’ll take your questions, of course. So, first, Cherie, to start with, you were diagnosed back in 2012. And I think you were traveling at the time, is that right?

Cherie Rineker:
No. I was actually going to school to become a natural esthetician before getting very sick.

Andrew Schorr:
In your professional background, I know you’ve been a triathlete. You’ve been a very active woman.

Cherie Rineker:
Yes.

Andrew Schorr:
And you’ve done a lot of different things. You’ve been a massage therapist but particularly active. So, it started with pain in your arm and your side, right?

Cherie Rineker:
Pain in my side, pain in my ribs and my sternum, in my back. I was a massage therapist, so I kept self-massaging myself
with tennis balls that I would lay on trying to find the right spot. And it just would go to different places. It would never ease up. It was just slowly getting worse and worse.

Andrew Schorr:
And this went on for like six months, you were going through all sorts of problems and fatigue.

Cherie Rineker:
Right, right. Yeah. Slowly, the fatigue was getting worse and worse, to the point that my daughter was 6, at the time, and I would still pick her up, and I couldn’t do that anymore. And I had a hard time climbing up the stairs to my apartment. I ended up having low grade fevers and a lung infection that just didn’t want to go away. And I was being tested for all kinds of things. Everything came up negative. This little word, cancer, started creeping in my mind. And that’s what it ended up being.

Andrew Schorr:
And you have lesions on your bones, right?

Cherie Rineker:
They were all over my rib cage, all over my spine and my scalp, on my pelvis, yes.

Andrew Schorr:
How old were you, at the time of diagnosis, Cherie?

Cherie Rineker:
I was 44 years old. But I really believe that I had some form of myeloma for years, because I remember at 40 feeling very fragile, in my bones. And I asked my gynecologist, if I could get a bone density test. And he asked me if I was still having regular periods. I said yes, and he said you’re fine, don’t worry about it. And I think that maybe they could have found something, at that time, already.

Andrew Schorr:
I have a question for Tiffany just while we’re talking about diagnosis. So, Tiffany, she was a pretty young woman. Often, we think of people older with myeloma. But really, there is an age range, isn’t there?

Tiffany Richards:
There is. Certainly, the median age is about 69 years of age. But we do see patients who are younger being diagnosed with myeloma.

Andrew Schorr:
Okay. So, Cherie, you had your diagnosis. It’s a shocker. So, since 2012, you’ve been through a whole range of treatments.

Cherie Rineker:
Yeah. They started out they were going to do surgery on my spine. I had plasmacytomas on T3 and T4, one at one end to the spinal canal, so they were worried I was going to be paralyzed. The surgery was too tricky, so they chose for radiation. And after that, I moved from Tempe, Arizona to Houston, Texas to be closer to MD Anderson and went through nine months of induction chemo, which we changed up I think three or four times. And the side effects got worse and worse. So, we went ahead with bone marrow stem cell, my first one, in August 2013, even though I still had 80 percent of my lung and my bone marrow. And four months later, I chose for a second stem cell transplant, which only brought my numbers down to 20 percent. And then, I’ve been on continuous chemo through December of 2017, when I told Dr. Lasky I am done with chemo. It was destroying my immune system. And I was just very sick. And that’s when I started searching for a CAR-T trial.

Andrew Schorr:
Oh, man. So, you’ve been through it. There are some people who have done pretty well with transplant. Some people even have had oral therapies or infused therapies. But for you, you kept running through them.

Cherie Rineker:
Yes. And I found out later I had translocation (11;14), which is not supposed to be very aggressive myeloma. But Dr. Lasky said mine was just very stubborn. And it just didn’t do good with medicine. I would have short responses, and then, I would relapse again. And that’s how I went through the 13 different regimens.

Andrew Schorr:
And so, you had testing many different times. But the news often came back not so good.

Cherie Rineker:
Yeah. Some months, it would go better than others. And I would have a graph, in my bathroom sink, just for positive affirmation. And seeing that go down to zero, my first one, I think based on that analogy, I was supposed to be in complete remission August of 2013, which, obviously, didn’t happen. And it was just so devastating every time to see the numbers go down for a bit and then, creep back up again. And going up, Dr. Lasky often said that sometimes happens. But after so many relapses, I knew, as soon as those numbers went in the wrong direction that meant I had become refractory, and I had relapsed.

Andrew Schorr:
All right. So, just for our audience, CAR T-cell therapy that some people have heard about for this blood related cancer and for some others now, too, remains experimental, in some areas. And some lymphoma is approved, but not yet in myeloma. But you entered a trial. And, so far, over nine months now, it’s worked out, right?

Cherie Rineker:
Yes. I got my CAR T-cells back on March 12. It’s my fourth birthday now, after my birth and two stem cell transplants. And I went through a serious cytokine release storm for about a week and then, came out and started feeling better than I had in years real quick. And about three weeks later, I had my first complete remission, negative, no Bence Jones in my urine, no kappa light chains, ratio good. And then, the first bone marrow biopsy showed complete negative. They couldn’t find any myeloma.

Andrew Schorr:
And you’re going to go back for another check up soon where we hope that that still goes that way. And I should just mention, some people have seen some things we’ve posted along the way, and Cherie has, too, where I was thrilled when Cherie sent me a picture. And having been really almost at death’s door, she was out gardening, right, Cherie?

Cherie Rineker:
Yes. I do everything now. I’m back to teaching yoga and meditation. I’m doing reflexology again. I’m going to the gym, for the last month, trying to get strength in my body and my bones and my muscles. I have weened myself off all opioids. So, my medicine cabinet that was just bursting at the seams before, now, just has three little things that Valtrex, we, I guess, have to be on indefinitely and a couple of other little things. But, yeah, I feel healthier than I did probably one or two years prior to my diagnosis. So, it’s really incredible.

Andrew Schorr:
This is maybe the new age of myeloma care, with a much broader range of treatments than we’ve ever had before. And for someone like Cherie where so many other treatments that have worked for some of you who are watching were not working for her. And Doctor, I’m sure, when you hear this story, that makes you feel great that medical science has advanced, in this way.

Dr. Manasanch:
Yes. It’s great that we can use our own cells to treat diseases, including cancer. I do think that, of course, these therapies are some of the major advances that we’ve had over the last five years. In fact, when the CAR-T cells were starting, I was a fellow at the National Institutes of Health. And the first patient that got one of those infusions was a patient with, actually, leukemia. And I was on-call that night, and I was called because the patient was getting a cytogram release, so I had to send this patient to the ICU. And the patient, subsequently, did all right, but this was many years before this was going to be done in myeloma.

And then, I remember very well, when I left NIH to come here, that was in 2014, one of the days I was leaving, I kind of ran into Dr. Korkendorfer who is really the person, the scientist, that has developed this in myeloma with targeting the BCMA antigen. So, he really should have a lot of credit for this. He’s the one that really started the identification of this target that now is used in many other therapies, as well in clinical trials, not just for CAR T-cells. And he kind of was waving to me and saying, “You know, I’m going to be starting this BCMA CAR T-cell study here. So, send me some patients.” So, this was back in 2014, of course. This therapy seemed to work very well. Unfortunately, most patients still do relapse from these therapies.

And so, this just means to us that we have to keep fighting to improve these therapies. So, these are still first generation of these therapies. I think that we can improve on them. And I think there’s a lot of research going on on that. Still there are some patients, like Cherie was saying, that are years out and doing well. So, I know that is not like this or everybody. But the hope is still there that we can improve on these therapies.

Andrew Schorr:
Okay. So, that brings us to testing. So, Tiffany, you’ve been working in myeloma for a number of years. You’ve done a lot of programs. The testing keeps getting better, right? But patients are saying to you, “How am I doing, how am I doing?” Like Cherie had the picture on the wall of the bathroom charting herself. Tell us about how testing is changing and this whole term of minimal residual disease. What does that mean?

Tiffany Richards:
Yeah, it’s a good question. So, when I started working here at Anderson 14 years ago, the light chains had recently been introduced. And we were starting to incorporate them into our response assessments. But, predominantly, we were looking at SPEPs and UPEPs. But, certainly, the light chains would give us an early indicator, if a patient was starting to relapse.

And then, over time, the response criteria have improved to now that we have minimal residual disease. And how I explain it to patients, I’m sure you’ve seen the slide with the iceberg. And patients, I think, relate to that. And I explained it to them that we pushed the iceberg far down below the level of detection that, with the most testing that we have, we can’t detect the iceberg anymore.

Andrew Schorr:
Okay. But that detection of cancer cells has become super sensitive now, right?

Tiffany Richards:
Yes.

Andrew Schorr:
So, okay, Dr. Manasanch, help us understand how are we assessing MRD? So, if you are working with a Pathology Department or whoever, what tests are they doing to determine whether a patient has been treated successfully, basically?

Dr. Manasanch:
So, we’re very fortunate here at MD Anderson because we have a fantastic flow cytometry lab. And so, we have minimal residual disease testing by flow cytometry. And that’s just sending aspirate of bone marrow, so just the blood and the aspirate, when you get a bone marrow biopsy done, and sending it for analysis through a special machine that really can look very carefully at the markers around the surface of the myeloma cells. And by looking at these markers, we can determine whether the plasma cells are normal or abnormal. And we can determine how many, in that specimen, are plasma cells and then, how many are normal and how many are not normal.

And so, if we do find any that are not normal, then, that’s what we call minimal residual disease in a patient that has been treated. So, if you have multiple myeloma, and you have been treated for multiple myeloma, it is very common to do not just the blood studies and the 24 hour urine but also to do a bone marrow biopsy. And when you do the bone marrow biopsy, usually, that’s when you take a sample for analysis. Now, that’s what we do here at MD Anderson. Basically, we can detect one cell in hundred thousand, which is the sensitivity people are always talking about 10 to minus 4, 10 to minus 5, 10 to minus 6. So, ours here, with our flow cytometry testing, is 10 to minus 5, which is quite good. And it’s probably almost the best that you can get with flow cytometry, in the bone marrow. And so, we get the result within a few days. And so, we’re very lucky with that.

Now, there is also another technique. There’s a company called Adaptive Biotechnologies. And they have a test that is FDA approved. It’s called clonoSEQ. And they have different versions. And the most recent one, actually, is quite potent. And they can detect cells one in a million. So, I’m not sure, Cherie, if I may ask you, in the test that you had done, did you have the clonoSEQ test done, with flow cytometry?

Cherie Rineker:
I just emailed my oncologist, the trial oncologist, about that. And he said that I was MRD negative, with the clonoSEQ
was 10 to the negative 6.

Andrew Schorr:
Yeah. Because it’s very difficult to get the 10 to minus 6. So, the level of sensitivity is, basically, how many cells can you detect, in a sample of millions of cells, how many can you detect that are abnormal with myeloma. And so, with flow cytometry, it’s very difficult to get to one in a million. So, that’s why I suspected that’s probably done with the clonoSEQ assay. So, that test, basically, is available. The doctor has to send a sample to that company, Adaptive. And then, what I’m not very clear on is how the billing is done. Now, for here at MD Anderson because we already have an assay that is set up, it really doesn’t cost extra to patients to do. We really do it through flow cytometry. And so, that’s really what we’re doing at MD Anderson right now is flow cytometry minimal residual disease. It works pretty well. We know, from many studies, that it is predictive of how long a remission will last, in most patients.

However, each patient is so different that this is something that, whether, in your particular case, you need minimal residual disease or not is something that really has to be addressed with every patient because every patient is a little bit different. And one of major limitations of minimal residual disease is that it comes from the bone marrow. And the bone marrow is a blind biopsy, right. And so, people can have other things in other places, and we don’t see them. Now, it seems that, for most patients, it still works pretty well. But if you have a collection of plasma cells somewhere else that is not in that specific location where we do the bone marrow, that’s not going to show up. And so, that’s one of the limitations of this. And what we try to do with that is you can combine some imaging with the bone marrow test. And that even has a better prediction probably. So, you can do like a whole body MRI or a whole body PET CT. And then, you can look to see are there any lesions, anything that we’re not looking at the bone marrow. But I’m definitely having minimal residual disease negative but one to one million, which is a very good sensitivity,
after CAR T-cell therapy is excellent. It’s fantastic.

Andrew Schorr:
Oh, good. So, you got a second opinion here, Cherie.

Cherie Rineker:
And I will say I had the PET scan done as well. So, my only concern is because I relapsed so many times and so fast, how durable is this one? Will this one pop back, too? So, there’s some fear attached still.

Dr. Manasanch:
But that’s so difficult to tell because every patient is so different. Every patient is so different. And this is where it’s very easy to take a study and say 50% of these patients did this, 50% did this. But when you have that patient in front of you, it’s so hard to predict the individual rates because you mentioned, for example, I your case, all you had was this translocation (11;14), which really doesn’t signal this that this is going to happen. But it happened. And so, it’s so hard, when patients say how long am I going to live. I don’t think that we can tell. We can say, based on average, for your case, maybe this is what could happen. But really, no one knows.

So, each case is very, very individual. It’s very different. You really have to look at all of the things carefully. So, it has to be very careful analysis of each case. And so, this is why we run into surprises. But, overall, it is true that, if you have—no matter what type of myeloma you have, if you have a complete remission with minimal residual disease negativity that seems to pretend a good prognosis, in terms of the time that you stay in remission. And so, that’s important. And that usually translates into people living longer, the more you stay in remission. That’s usually how it goes. But, again, that’s a generalization. And every patient is very different. So, it’s just hard to do case by case.

Andrew Schorr:
And I want to ask Tiffany, so, Tiffany, you have patients come to you for follow-up care. And tests have been ordered along the way. And you’re going over the results with them. So, if it were me, and I had this, in my condition, chronic lymphocytic leukemia, where Dr. Wierda was also there at MD Anderson said, “You know, you’re not MRD negative.” And I was kind of crestfallen. And I said, “What does that mean?” He said, “You’re going to need treatment again sometime,” kind of like what the doctor was just saying, “but we don’t know when.” And for me, it was many years, actually, for that particular condition. But tell us how you described that because I’m sure you’ve seen people disappointed or feeling pretty good. So, how do you manage that, with your patients, Tiffany?

Tiffany Richards:
Yeah. I usually try to set expectations, right from the beginning, when a patient first comes in because all patients want to have a CR. And they all want to have the deepest remission possible. That being said, I tell them upfront that the majority of patients may not get there. But that I have patients who have never achieved a complete remission. And they’re living 20 years later. So, I always tell patients that, at the end of the day, we have statistics. And we use those to formulate our treatment plans. But they’re their own unique case. And, if you don’t get to that MRDnegative status that it’s not the end of the world, that it doesn’t mean that all hope is lost and that this is the worst thing on earth. So, I try to set that expectation right from the beginning, so that, if they don’t get it, they’re somewhat prepared for that, and that they don’t leave feeling super, super disappointed.

Andrew Schorr:
I want to remind our audience, if you have a question, and some people, certainly, have sent them in, just send it in to
myeloma@patientpower.info. Now, Doctor, let me ask you this. So, here’s the thing. You’ve got all of these variables. So, it sounds like the testing is one indication. But what are the other things you’re looking at? It seems almost like a constellation for you, as a practitioner, to know how is somebody doing. Or even, if you’ve had a certain treatment, how is that treatment going. So, tell us what else you look at. So, the MRD testing to the 10 to the whatever, 5 or 6, as you can, what else? How do you assess how somebody is doing?

Dr. Manasanch:
Well, so, the first things that we do is we have what we call our myeloma labs. And the myeloma labs include something called electrophoresis. That’s a test that looks at each patient’s individual paraproteins. Those are the proteins that the myeloma makes. So, most myelomas, about 80 percent to 85 percent make what we call—they make an immunoglobulin. And those immunoglobulins, they actually have two parts. They have a heavy chain and a light chain.

That’s how immunoglobulins are structured. And those immunoglobulins usually fight infections. But the immunoglobulin that the myeloma cells make does not fight any infection. In fact, I’m just going to go in there and say that we have some exciting research here where we’re going to be looking at whether these paraproteins target in myeloma. So, we don’t know what they target. In a healthy patient, an immunoglobulin is supposed to target an infection or something that is foreign to us. And, usually, it’s viruses, bacteria, and so on.

But in myeloma patients, we don’t know. And we’re trying to look into that to see what is going to happen with the etiology of myeloma. Now, that’s what we look at in the blood, so those immunoglobins, those paraproteins. About 10% or 15 percent of patients, they don’t have the heavy chain. So, they have only one part or two parts of the structure of immunoglobulin. Instead of having the heavy chain and the light chain, in the immunoglobulin, they just have the light chain.

So, when I say this, it may sound a little complicated, but it’s really very easy. Most myeloma patients, they have an immunoglobulin G. So, we look to see how much of the immunoglobulin G is in the blood. Some patients will have immunoglobulin A, some will have immunoglobulin M. Maybe one percent of patients will have immunoglobulin E or an immunoglobulin D as in David. Those are very rare, but we see them. So, that’s usually most patients, myeloma express some of those. So, that’s a nice way you can correlate how much tumor you have, how much myeloma you have, by how much of this protein is in the blood.

Usually, most of the time, you can correlate that pretty well. So, the higher the level is in the bone marrow, the higher it is also in the blood. And so, usually, with a simple blood test, you can already know a lot about the patient’s myeloma, if the levels are very high or not. So, the first thing we look at, again, is this electrophoresis.

And that tells us how much of those immunoglobulin are in the blood. And then, we have, also, the light chains, which are kappa and lambda. So, we look at those. Those are the second part of the immunoglobulin. And, again, about 15 percent of the patients, they don’t have the heavy chain. They don’t have the immunoglobulin G or D or M. They just have the light chain, kappa or lambda. So, patients that have the whole protein, the whole paraprotein, the whole immunoglobulin, both the heavy part and the light chain part, we look at that through electrophoresis. And that’s very useful. And that’s how we determine the response.

So, you have the patient that has an immunoglobulin G kappa myeloma, that’s what the myeloma is making. And they start with a number of four. So, even if that number goes from 4 to 2, that’s a partial response. If it goes from 2 to 0.4, that’s a very good partial response.

And if it goes to 0 that could be a complete remission. So, really, most of what you need to measure like partial response, very good partial response, is really just the paraprotein. If you have a light chain myeloma, then, you have to look at the light chains in the blood. So, you don’t look so much at this paraprotein and the electrophoresis, but you look at the light chains. So, basically, you need, for someone who has the regular myeloma like most people have that has both heavy and light chain, you just look at the electrophoresis. And that can tell you a lot already. And that’s just one test.

Then, if you want to know about complete remission, once you reach that zero, then, you have to look at something called immunofixation that tells you the type of paraprotein. You have to look at the light chains. Also, you have to look at the variations in the light chains in the blood. And you have to look also at the urine. So, usually, that’s what we do with each patient.

So, there’s a lot of tests involved in this. So, the urine, the best test to measure the urine, in myeloma, is still a 24-hour urine that measures how much of the Bence Jones protein, which is the myeloma protein in the urine, varies. And that can be done quite easily, although it’s a little bit cumbersome for patients. And you look at that. So, only once you reach your complete remission, once the numbers in the blood are negative, the numbers in the urine are negative, then, usually, that’s when we say, okay, we’re going to do a bone marrow biopsy.

And then, if the bone marrow biopsy is negative, the bone marrow is normal, then you can do your MRD testing, your minimal residual disease testing. And that’s how the levels of remission. However, it gets a little bit tricky because you can have a patient that has still some paraprotein in the blood. So, the blood markers are positive. The urine markers are positive. And then, you do your bone marrow, and you do your minimal residual disease testing, and that is still showing a little bit of the—sorry, that is, basically, negative.

So, you can have an MRD-negative test. And you can have patients having some paraprotein in their blood. Okay. The main explanation for this is because the paraproteins, the IgG kappa mainly, takes a very long time to disappear from the blood. So, you may actually be looking at the bone marrow, and you don’t see any myeloma in the bone marrow, and that’s actually a good thing. What it likely means, for most patients, is that, with time, what they’re seeing in the blood will go away. So, it does seem that the IgG kappa tends to linger in the blood.

So, if you have patients here that have IgG kappa, and they have a minimal residual disease testing in the bone marrow, and that is not normal, and they still have a little bit of their IgG kappa in the blood, then, it is likely that this will actually go away with time.

Whereas, if the MRD testing is positive, it is a little bit more difficult. So, it can give you chances. But, basically, there are a lot of tests that we use.

Andrew Schorr:
Wow. So, I want to say, first of all, thank you for that because ladies and gentlemen watching are living with myeloma. Now, you hear how complicated this is to really understand, maybe not for Dr. Manasanch, but for some, particularly community oncologists around the country, around the world, to really help you get a clear picture of what’s going on with you. And this whole thing about lingering of some of these paraproteins where you’ve had an MRD negative test, I’d say, oh, I have an MRD-negative test. And then, if this other one came up, I’d say, oh, my God, could you explain the linger. And it’s maybe not such a big deal, right?

Dr. Manasanch:
It doesn’t have to be a big deal. And, usually, it still is a good thing, if you have still a little bit of protein in the blood and they myeloma.

And then, the bone marrow is normal, and the flow MRD or the clonoSEQ is negative that usually, probably, means that it’s just taking you a little bit longer to clear that protein from the blood.

Andrew Schorr:
Wow. So, Tiffany, the doctor rattled off a whole bunch of testing and light chain, heavy, light. If somebody is diagnosed with myeloma, and I’m sure this—Cherie, you’ve sort of gone to school learning this, over the years, but it is overwhelming to try to understand this. Obviously, you have to have a healthcare team you trust. How do you help people through this? Because they want to know how am I doing.

Tiffany Richards:
Right. That’s a good question. I think you’re looking at your patient in front of you. So, you’re going to tell them what they need to know, what our goal for them is. So, if they don’t have light chain—if they have a regular myeloma, you’re going to talk about their M protein and what we want to see their M protein go to.

And so, you’re not having to like go through everything all at the same time. Usually, the physician I work with will explain the iceberg discussion to the patient, at their initial visit. But, obviously, there’s a lot of information that’s given to patients, at that point in time. And so, you’re really just trying to take it—I try and take one step at a time, with patients because I find that they get very overwhelmed with information overload. And so, trying to break down that information, I think, is useful for patients, rather than giving it to them all at one time and just reiterating to them, at each visit.

Andrew Schorr:
Good, thanks. So, Dr. Manasanch, what do you tell patients? So, again, you’ve said, well, we’re going to do this test, or we’re looking at these proteins or light chains. How do you help people work with you to have confidence that maybe things are working?

Dr. Manasanch:
Well, I know it seems complicated, but it’s really very easy. The way we have our results, at MD Anderson, is it comes through the paper sheet that has all of the results there very clearly. And you can really point out, okay, this is your result. This is the number. This is your starting point. So, I just say this is your starting point. This is your number. Now, we want this number to go to normal. For the M protein or paraprotein, the normal number is 0. So, we would like the number to go to 0. That’s what we would like. Now, not everybody goes there. What does it mean? Well, for some patients, even if they don’t get there, it doesn’t matter.

They still do really well. For some patients, they don’t. Do I know, when I look at the patient? I cannot know. So, then, I don’t think that it’s very important because I pay a lot of attention to the things that I know that will impact.

So, whereas it is true that, for most patients, it is better for these M protein or these paraprotein to go to 0, there are some patients, as Tiffany said, that it never goes to 0, and they’re still doing great. And they don’t need anymore treatment. Some of them, they have the same number, zero point something, for years without treatment. So, it’s very difficult to say. So, I think it’s very important. The way I explain it is that we want this number to go to 0 if possible. If it doesn’t go to 0, then, we’ll talk about what to do, at that time, and whether we need to do something for your case or not because everybody is different.

And the people that have light chain disease, which is measured through the light chain test, then, I just go and say, okay, this is the light chain. This is what you have. We want this number to go to normal. Normal is around 10 to 20, something like that. We want this number, which is the ratio, to go to around 1, 1, 2, 3, something like that. And that’s our goal. That’s what we’re going to try to accomplish.

And then, when this number—I don’t go and explain all of this and MRD in the first visit because it’s too much. It’s just a lot. And patients with myeloma, they become your friends because the come to see you really every month. You see them all of the time. So, you have so many opportunities to talk about those things in follow ups that I just say the goal is to get you better, get those numbers reduced. And then, we’ll go and see from there. And then, in subsequent visits, then, we discuss, okay, well, guess what. This number is close to 0. Or we’ve done already a few months of treatment.

How about we do a bone marrow biopsy, and we look at minimal residual disease. And then, I discuss that. So, that’s usually how I do it. We break it down a little bit. And I don’t go into so much detail. But the patients always have all of their results. I usually give all of the results to my patients, so they can process them. They can look at them. They can become familiarized with them. I think it’s very important for patients to know what they’re looking at, what results they need to be aware of. And so, I certainly point to that probably at every single visit for every patient.

Andrew Schorr:
Okay. Cherie, what were some of the test results that you were following closely for you to feel how you were doing?

Cherie Rineker:
So, for me, I never had an M spike. And so, I guess that means I didn’t have the heavy light chain. Did I get that
correct?

Dr. Manasanch:
Yes, that is correct.

Cherie Rineker:
Okay. So, I never had an M spike. I believe my kappa light chain started out in the tens of thousands like 17,000, and my Bence Jones was around 8,000. And so, I was very afraid of chemo. I did my first month of lenalidomie (Revlimid), dexamethasone (Decadron) and bortezomib (Velcade). And my kappa light chain, actually, went up, after the first month. But we had a little accident at MD Anderson.

I had not put the lid good on the 24-hour urine. And my husband picked it up, and half of it ended up in his shoe, which got him very upset. But when we went to Dr. Lasky the next time, Dr. Lasky kind of gave me a high five on the Bence Jones. He said, “I don’t understand because your kappa light chain had jumped like 1,000.” He said, “But your Bence Jones went in half.” And I was very out of it. I was on a lot of medicine, at that time. And as an afterthought, I said, “Well, we did lose half the bottle of urine.” I told him the story. And I remember the look on his face went from, okay, this is a good thing to concern.

And looking back that little accident actually probably saved my life because being a holistic practitioner and being so afraid of chemo, probably had I known that both of the numbers had gone up, I probably would have said I’m not doing this anymore.

See, I’m right, and chemo is not good, and we’re going to stop it. So, the next month, the numbers slowly started coming down. They didn’t do a bone marrow biopsy for me. Well, they did one, and it was inconclusive. And then, they did another one, nine months later, before my stem cell transplant, which then showed 80 percent in the bone marrow. And I had asked Dr. Lasky what is a good way to go into the stem cell transplant. And he said, “We like patients to be between 0 and 5 percent.” So, needless to say, when I heard 80, I was pretty…

Andrew Schorr:
…you had quite a journey. So, we’re going to take some questions, in just a minute. Caroline has already sent one. Caroline, stand by and send them to myeloma@patientpower.info. So, Tiffany, some of the testing is to see what subtype of myeloma you have. Dr. Manasanch was talking about that.

Do you have this type of myeloma or that type of myeloma. So, some of the testing is related to that. So, is that sort of
step one is to see what’s your myeloma and how do we measure that? Is that where you sort of start?

Tiffany Richards:
Well, when you’re looking at an M protein, you do have to know what type of myeloma that they have. And a lot of patients, particularly patients who are active on blogs and support groups and stuff, always want to know what type of myeloma do I have. And so, the immunofixation will tell us what type of protein is being produced. So, whether it’s an IgA kappa or an IgG kappa, or in the case of a urine protein electrophoresis, it will tell us if it’s a kappa or a lambda. And then, we look at the M protein as well.

And I wouldn’t say there’s a Step 1 that we look at and then a step two because I think, when you’ve been doing this for so long, it’s more fluid than that. But that’s what patients want to know is what type of myeloma do I have.

Andrew Schorr:
Okay. And then, just to be clear about the MRD testing, which becomes more and more sensitive, is that really kind of later in the process to do the MRD test? Where does it fit in?

Tiffany Richards:
Yeah. So, usually, the MRD testing is not going to happen, until the patient is in a good remission. And so, generally, if the patient has achieved a complete remission, or if they have a small amount of residual protein, then, you may consider doing it. It really depends on the patient situation and where they are, in their journey.

Andrew Schorr:
Okay. What about do it more than once? Do you get a remission, but then, later somebody comes out of remission? And later, would you do it again?

Tiffany Richards:
Generally, for a patient who is not on a clinical trial, at this point in time, we may recheck it. But for the physician I work with, we, generally, won’t recheck it because, at this point in time, it’s not like we would change—so, if a patient is on maintenance, lenalidomide, for example, and they achieved an MRD negative, and now, they’re MRD positive, but everything else is still looking okay, their numbers aren’t changing, we wouldn’t necessarily change treatment, at that point.

And so, it’s really going to be patient dependent. Sometimes, you’ll get them once a year, but, again, we don’t necessarily change treatment because a patient went from an MRD negative status to an MRD positive status.

Andrew Schorr:
Okay. Doctor, do you have a comment about that, about how often do do MRD or when?

Dr. Manasanch:
Right now, if you are on a clinical trial, the clinical trial, basically, tells you when you’re going to test for this. If you’re not on a clinical trial, I’ll tell you when I do it. And I think also, a lot of physicians do it at MD Anderson, which is usually before our stem cell collection.

So, newly diagnosed patients, they come in. Okay, yes, we confirm this is myeloma. This needs to be treated. They get treated. The response rate for the treatment of multiple myeloma right now, with the therapist that we use at MD Anderson, the response rate is 100 percent. So, basically, everyone, maybe 1 patient in 300 doesn’t respond. So, we can say response rate is 100 percent. So, all of them are going to respond or almost all of them. And then, we get ready. Most of the times, most patients actually, in our center, about 80% of newly diagnosed patients choose to do an upfront autologous stem cell transplant, which means that they need their cells collected.

And they proceed to get high-dose melphalan (Alkeran), which is the medication that is given with that transplant process. And so, we check the bone marrow to make sure that, actually, we’re not going to pick up a lot of bad cells with the stem cells.

We check the bone marrow because we also want to have a good response, whatever response you have, usually, before a transplant. The marrow transplant outcome, again, for most patients, but generalizations do not apply so well to individual patients and their cases. So, every patient is different. But, usually, we check the bone marrow biopsy, before we do the stem cell collection. And then, the bone marrow biopsy, after treatment, usually includes a minimal residual disease testing. So, that’s definitely something that we kind of consent to do at MD Anderson.

After that, it really is physician dependent. And it’s also patient dependent. So, all of us have a patient who wants to have a bone marrow biopsy every year and have minimal residual disease testing and seeing is it coming out of remission or not. Right now, there is no evidence coming from a clinical trial that that’s going to add any benefits.

So, for example, doing a bone marrow biopsy once a year to see the minimal residual disease, whether it’s positive or negative. We don’t have information on that. However, from our experience, I believe that we will be doing this in the future. So, patients will get minimal residual disease testing in the future. And that will determine what we do with treatment. Why? What Tiffany said. First of all, it’s common sense. It’s a little bit of common sense. But all of the studies, all of the evidence that we start having from clinical trials will be showing is that the earlier you know and the earlier you do, the patient seems to have better outcomes.

And that translates to smoldering myeloma, hopefully. So, now, I keep hearing more and more stronger voices about
maybe treatment of that. So, that’s a big area also in myeloma. Why?

Because, as Tiffany said, they use the paraproteins, the electrophoresis, the M proteins. And then, they have the light chains. And the chains are a little bit more sensitive. So, then, now, we don’t wait. So, the patient has a paraprotein, an M protein, of 0.0, and then, we don’t wait for that paraprotein to be 1, if the light chains are high. If a patient has the light chains are going up, we treat the patient, if they’re consistently going up. We don’t want for the paraprotein to be a certain number. So, I feel like a minimal residual disease would be something similar.

I feel like patients who will have the minimal residual disease, if they’re minimal residual disease is negative, they will have the testing done. And if we see that that starts to change, maybe the frequency of the MRD is increase. So, now, instead of doing your minimal residual disease testing every year, now, because it turned from negative to positive, now, we’re going to check it again in three months.

And guess what, if, in three months, that’s also higher, then, maybe you change the treatment, or maybe you start treatment. Now, that’s in the future. That’s what we are hoping to achieve, with all of this. And I think that a lot has done in the last few years. I believe that the Food and Drug Administration, the FDA, will actually approve minimal residual disease as an end point for clinical trials. So, basically, the response how drugs are going to get approved is not going to be just, if your remission is longer or if you live longer. But if you get drug A versus drug B, in a clinical trial, what is the percentage of patients that are minimal residual disease negative. This is going to happen. And so, right now, the use of MRD, I think, has either been limited to when we do our bone marrow biopsies in patients after treatment and the significance is prognostic. So, overall, for most patients, if you’re MRD negative, it’s better than if you’re MRD positive, again, for most patients. And that’s all that we can say right now, today, is prognosis. But in the very near future, I think that we will do things like changing treatment. Maybe we’ll do things like stopping treatment. I don’t know. But we have a lot of studies that are looking at this right now. And they will report, in the next few years. So, this is where all of this is going. And right now, MRD is limited, I think, it prognosis. If you want to know your prognosis. And then, if you’re MRD negative, and you have to have it tested every year, you can. There’s nothing against it. What do we do with the information, if it turns positive?
It’s a little bit ahead of the time where we have full answers. But it depends on the patient and the physician a lot.

Andrew Schorr:
Okay. This was a very complete answer. So, questions are pouring in. So, we’re going to start getting a lot of questions. Just so I understand, so the MRD testing today is only from the bone marrow, or can it be done from the peripheral blood, too, doctor?

Dr. Manasanch:
That’s a great question. Right now, it’s only from the bone marrow.

Andrew Schorr:
Okay. But that may change.

Dr. Manasanch:
That may change. We, actually, have a study here at MD Anderson that I hope is going to be starting by the end of the year, which is going to be looking at something called the single cell assay, looking at, basically, each myeloma cell in the blood and doing very complete analysis, anomic analysis, something called proteomic analysis, looking at how the different cells are a little bit different. I think that, in the future, we probably will be able to do a blood test. We are not close to it yet. So, I don’t think, as I tell you, MRD, FDA approval for regulatory trials, I think, it will be soon. MRD testing, for the treatment decisions, soon, sooner rather than later. Maybe a test in the blood, maybe not so soon. So, maybe a few years.

Andrew Schorr:
You need a crystal ball. Okay. So, Tiffany, I think we’ve been talking about when MRD testing is typically done or when could it be done. And then, so Matt says, “What about the cost?” So, how do you guide people. Where does the cost come in, Tiffany? What are the costs of MRD testing?

Tiffany Richards:
Yeah. So, I know that Medicare will now pay for MRD testing, but that doesn’t necessarily…

Andrew Schorr:
…you said they will pay for it?

Tiffany Richards:
Yeah, for the clonoSEQ, they will pay for MRD testing, Medicare will. Whether or not other insurers, I have not heard from any of our patients that they’ve had difficulty or that they’ve had denials or that they’ve had to pay out of pocket. So, I think, by and large, insurers are reimbursing.

Andrew Schorr:
Okay. Now, some of these questions, folks, I don’t have myeloma, so I’m not as well versed as some of you, but let’s do
this. Matthew asked, “If you have M protein 0.1 or 0.2, should you get MRD testing?” And otherwise, you have negative numbers. So, Doctor, he’s wondering, with a 0.1 or 0.2, the M protein, should he have MRD testing?

Dr. Manasanch:
It depends. So, a patient that has—so, just a generalization. A patient who has very little paraprotein in the blood, assuming this I like a regular myeloma, most of the myeloma types that have both the heavy and the light chain. And then, you have 0.1 and 0.2. So, the response for these type of patients is usually what we call a very good partial response. Why? Because most myeloma patients that have this type of myeloma, the M proteins or paraproteins, they’re in the range of 3 or 4 or 5 grams, when they start. So, by the time they reach 0.1 and 0.2, that’s already more than a 90 percent decrease. And that’s what we call a valuable partial response. So, if you have a patient—if you’re a patient, and you know that your response is a very good partial response, does it make sense to test for minimal residual disease for prognosis?

It makes sense, for what I mentioned. Actually, if we look at the patients who are in very good partial response, and we look at MRD positive or negative, the patients who are negative tend to do better, in terms of how long their remission will last. So, if you have—you are in very good partial remission, and you want to know if this test if the clonoSEQ or if the flow is going to find any myeloma cells or not, if it does not find any myeloma cells, if you do not have myeloma cells that the test can find, that’s usually better than if the test finds some for patients in very good partial response.

So, what happens is do you want to test for it in partial response. Well, let’s say it’s not 0.1 or 0.2, the protein is 1.5, it can still probably predict. But, at that range, most patients be positive. So, it really starts to make sense, when you have very little in the blood, very little protein in the blood, and a very good partial response or very good partial remission range or complete remission. That’s when you can actually discern. If you test diagnosis or if you test partial remission, most patients will be positive. So, you can test, but it’s going to tell you what you already know.

It’s positive. So, then, what’s the point. So, for this patient, if it is a very good partial response, if the response is a very good partial response, it makes sense to, basically, talk to your doctor and say, okay, is this something that we need to do or not. Because it’s only prognosis, it’s really just to know. It’s not going to—it’s probably not going to change.

Andrew Schorr:
I think Matthew wants to know, and I’d want to know, too, because you have those very low numbers. I think, to get our head on straight, wouldn’t you agree, Cherie, you want to know?

Cherie Rineker:
Yeah. Just for peace of mind.

Andrew Schorr:
All right. Let’s get to some more questions. So, Valerie wrote in. She said, “If I’m declared MRD negative, is there still a need to take maintenance therapy indefinitely?” So, Doctor, do you want to take that one?

Dr. Manasanch:
So, the first thing is that my first inclination to that answer is, right now, we’re November 19, 2018. So, as of November 19, 2018, today, yes, you have to continue, even if you are MRD negative because being MRD negative, all it means is that the test cannot find the cells. But we have a problem in myeloma. We have a big problem in myeloma. And in myeloma, we really cannot seem to cure it, for most patients. Which means we cannot get rid of it. It’s still there. So, our worry, when patients come out of therapy, especially if they’re doing well with their therapy, right, it doesn’t have a lot of side effects, and they want to come off of it just to come off of it or because you’re MRD negative, the problem is, okay, what’s going to happen.

So, I actually had plenty of patients to where complete remissions, MRD negative by our flow cytometry, and I’ve taken them off therapy because they’re older patients. And this is relapse because there’s really, it’s the discussion because they’re coming, and they’re not doing well.

They get admitted. They have infections. They are not doing well. So, then, okay, well, everything looks good. Let’s give a break. And the myeloma comes back. And then, you treat it again, and it goes into another remission. And then, it comes back again. So, being minimal residual disease negative, in relapsed myeloma, you still need to treat it.

Andrew Schorr:
Okay. There’s an elephant in the room here, though. Cherie, so with this 10 to the 6, you’re negative. The most sensitive test available. You’ve had the leading edge of treatment, CAR T, and yet, you’re hearing the doctor say we don’t think we are able to cure myeloma and that it may come back. So, you’re hearing this. What are you thinking?

Cherie Rineker:
Well, I belong to a CAR T Facebook group. And, sadly, there are people who have relapsed. There are people that have passed since relapse. And I have pretty severe post-traumatic stress syndrome, from everything that I’ve gone through from the many relapses. And so, I’ve noticed the further out I get, the worse my anxiety is getting actually not being on any treatment. So, hearing this, again, I feel that, at this point, maybe I want to go on maintenance. But I think it would disqualify me for the trials. And I want to be part of helping the CAR T research. At the same time, I can’t fathom the thought of having to go through another relapse.

And for me, even though the numbers are really small in the end, the plasmacytoma 9 centimeter, which popped out of nowhere, within a month, the cancer was so aggressive. So, would you recommend, doctor, that I should pursue a maintenance regimen?

Andrew Schorr:
But you’re in the trial though to see how long it lasts though, too.

Cherie Rineker:
Yeah.

Andrew Schorr:
Well, I think I’m just going to comment on this. First of all, I think Andrew’s question, so this maintenance usually applies to newly diagnosed patients, right. But I made my case with relapse because what happens, newly diagnosed patients, usually, the therapists we have now are so good. Most of the patients do really well, right. I think that this is the main thing of the webinar is patients with myeloma do really well right now. I think this has to be that, most patients do, okay? Once the myeloma has come back, and it has come back a few times, it just takes less time to come back.

So, my experience with doing minimal residual disease testing has been that. You can have somebody who has relapsed myeloma who is MRD negative. That does not mean that they’re always going to stay like that. But that also doesn’t mean it has to com back. I’m just saying that it can be either way. But for maintenance like after transplant or maintenance after your initial treatment, when you’re doing just continuous therapy, probably the right thing to do is to continue, even if you’re negative, continue that therapy because we really don’t know.

We don’t have data. There are studies now where, if you are MRD negative, they stop the therapy. And if you’re positive, they continue. Right? And, in fact, you’re negative, some patients stop, some continue. So, basically, we’re going to see, in the next few years, if you can stop it, if you’re MRD negative, if you can stop the maintenance. But right now, there’s no evidence, specifically, for your case, after CAR T. There is no evidence, right now, that starting therapy will make it last longer. So, probably , you don’t have to do anything. But for the newly diagnosed patients who go on the maintenance, they’re negative. Basically, that’s not affecting how we treat. It’s just an information. It seems like that’s a very good prognostic factor. But whether we have to stop the maintenance, that’s up in the air. And for most patients, I would probably say don’t stop it. Continue it. until we have at least some studies saying that, okay, if you’re negative, you can safely stop it. That’s what I would do. I’m just going to play a little bit devil’s advocate.

Andrew Schorr:
I would just say that, for me, just listening, there’s an old phrase don’t mess with success. Right now, you’re living your life. You’re going to go from—when you’re in a trial, part of the thing with the trial is to understand how long can you have this. Here’s a question we got in from Darrell. And, doctor, I think you answered this, but I just want to make sure. So, he said he did have a very successful CAR T, and all markers of disease in the bone marrow were zero. PET scan analysis, no evidence of rival disease. But the M spike, after 90 days, has remained 0.1. Is it possible, and I think he said this, that the M protein just takes a little while?

Dr. Manasanch:
It’s possible. It’s possible that maybe there are some cells that are making that M protein somewhere. But, again, as
long as the cells don’t get worse, who cares? If you have an M protein of 0.1, and that’s not making you sick, and it’s
going to stay 0.1 for 10 years, that’s not going to kill you. An M protein of 0.1, that doesn’t get worse. So, the key here
is, if you stay there, that’s okay. The problem is, if it goes from 0.1 to 0.2 to 0.4 to 1.0, That’s when we get into trouble.
If, for some reason, there is the balance of your body or immune system is just letting some cells be there and make a
little bit of protein, and that’s it, that’s great.

That’s all you need, to not get into trouble, with the myeloma. So, that’s possible, of course. You can have everything negative and a little protein, and the light chain is a little bit high. That happens. But it could just be that it’s just lingering a little bit longer. It could be that there are some cells making it that are not doing much. It just has to be followed.

Andrew Schorr:
Okay. Just to be clear, Darrell asked a follow up question. After CAR T, then, why not start a maintenance treatment,
even if you’re MRD negative? So, is that what is the protocol for the CAR T? Or what are you doing at MD Anderson?

Dr. Manasanch:
Well, that’s a very good question. I think that’s probably like the next generation of studies, with CAR T. So, right now, when we design clinical trials, you have to, basically, make an end point, right? So, what’s your goal, when you do a study? What do you want to prove? What are you trying to say about this?

And they do studies with CAR-T cells really mostly have two end points. One is safety. So, make sure that you’re going to give the cells. People are not going to die from toxicity. They’re going to actually going to be able to go through with this. And then, the second one is how effective is this, so what are the responses? How long does it take after a response for the myeloma to come back? So, those are the main things. So, if you do a CAR T, and then, you put a therapy right after, it’s very difficult to isolate the effect of the cell therapy. So, you, ideally, want to do a study with cell therapy that is just a cell therapy.

Now, once we have established that this cell therapy is safe, and the CAR Ts are safe, and they are effective, then, the
next generation of studies is you can add things to it. Usually, we have to build on things. So, you have to have a basis.
So, right now, there are already studies looking at comparing CAR-T cell to standard therapy.

So, for like patients that are not just relapsed after 10 lines of therapy, patients that have relapsed a little bit sooner, maybe like second lines, first or second relapse. You can get CAR T, or you can get another therapy. And then, basically, this is something that has to be studied. There is no data, right now, that I’m aware to do any therapy after CAR T cell. So, that’s why people don’t do therapies because we have not gotten to it yet. So, that’s a good question. Somebody is probably doing a study right now doing therapy after CAR T cell. But I have not seen any results from any studies like that.

Andrew Schorr:
Tiffany, here’s a question that came in. This person, they’re anonymous, don’t know if it’s male or female. I’m 55 years
old, and I’m MRD negative after 1.5 cycles of treatment. My doctor wants to do stem cell collection but possibly not yet the transplant. Does MD Anderson ever skip the stem cell transplant and just freeze the cells, just wait?

Tiffany Richards:
Yeah. Certainly, there are some patients that we do that that, if they are MRD negative that would be a possibility. But, again, I think that’s a discussion with your physician because there’s a lot of other factors that come into play, such as what are their chromosomes, are they high risk, standard risk, their level of presentation, what the PET looks like. And so, it’s really going to be patient dependent.

Andrew Schorr:
Okay. doctor, here’s a question, and maybe you can decipher this for me because I’m not that familiar with it. Nicole writes in what is your experience with the presence of only oligoclonal bands? Can it ever be a band sign? I’m nine months out from stem cell transplant. And the M protein went from 0.06 to the bands in the last one.

Dr. Manasanch:
So, oligoclonal means that it’s normal. It’s like your normal immunoglobulin. So, that’s usually a good sign. It means usually the sign of deep remission. So, that’s a good thing. What that means is you probably have a deep remission, which is usually either very good partial remission or a complete remission. And what it means is that you’re normal, you’re actually starting to have normal plasma cells in your bone marrow that are actually making normal immunoglobulins. And so, the pathologist, when they look at your electrophoresis and your immunofixation, they’re seeing that there are normal immunoglobulins. And they just say, okay, we see some bands in this test. And these are probably just normal bands. So, that’s a good thing to have.

Andrew Schorr:
Okay. Tiffany, so, we’ve been talking a lot about CAR T. And I just want to help everybody understand what it is because it’s been very much in the discussion of myeloma for people like Cherie who needed lots of treatment. How do you explain CAR T to people?

Tiffany Richards:
It’s a good question. What I explain to them is that because a lot of patients have already had stem cells, so they’re familiar with having their stem cells collected. So, I tell them it’s similar to that, but we’re going to collect your T cells. And T cells are a type of white blood cells. And those cells will then be collected and sent to the company where they will manipulate the T cells to go after the myeloma cells. And that they will get chemotherapy prior to having their stem cells reinfused. And then, their stem cells will be reinfused. So, a lot of patients, they’re pretty familiar with it because they’ve all had stem cells.
So, they get chemo. And then, I’m going to get the stem cells. And so, that’s usually how I explained it. I try to keep it pretty simple, for them, because it’s quite a complicated process.

Andrew Schorr:
Right, okay. And so, where are we now, Cherie? You went through it. And so, for you, it was kind of the leading edge because you, I don’t want to say you failed the treatments, the treatments had failed you. And so, this was really your last hope, right?

Cherie Rineker:
Yes, it was. The last time I remember going to MD Anderson and talking to my oncologist, and he said, “Well, we can now go to four different medicines, instead of the usual three.” And he’d had a couple of patients, and it seemed successful. And I just knew my trend. And, at that point, I needed monthly platelet infusions and filgrastim (Neupogen) shots constantly. So, it was both the chemo and the cancer were destroying my body. And I had heard about CAR T. And I said I’m done with chemo. I want to really pursue the CAR T, which, sadly, at MD Anderson, they started it I think a week after I had my cells returned to me. So, it’s been a 14 -our flight or $500.00 ticket to…

Andrew Schorr:
…there’s an element, as these trials open up. So, I just want to go—first of all, we do have time for a few more questions. So, send them to myeloma@patientpower.info. And I mentioned Caroline a long time ago. Caroline, I didn’t want you to feel lost. So, let me see if I understand. She says, “How will knowing disease state or using MRD measurement technology change treatment plans?” So, Doctor, I just want to understand. So, what do you do with the information? So, somebody says what’s the prognosis, is it changing what treatment you use or when, based on the MRD results?

Dr. Manasanch:
We don’t have any evidence to change treatments. So, these are all questions that need to be answered, in the next few years. So, the question of, if you are in complete remission, MRD negative, and then, you get another test done, and you go from negative to positive, do we start treatment, if you are not on treatment? If you were on treatment, do we switch it? All of those things, and how often do we test for it. We don’t have an answer for those questions. We really don’t have a guidance for that. So, it’s really just, when we test for it here, it’s just so because the technology is available.

And we know that it’s prognostic. So, we know that patients that are negative, they seem to do better. So, it’s nice to have the information, but there’s not much that we can do with it, right now, except just make someone happy telling them this is already negative. But there’s not much that you can do with information. And that’s why Tiffany was saying, Dr. Weber, ewe don’t do it, unless—we test after treatment.

And every time after treatment, we test for it. And if it’s negative, okay, we know that’s the best level of remission that we have. But what does it mean, in terms of treatment? We don’t know that. So, a lot of centers don’t even do MRD.

Andrew Schorr:
Okay. Yeah. So, that’s my next question. So, we have people all over the world watching. So, Cherie has been a patient of MD Anderson. She also went over to Nashville. They have a big center there. These are major centers. But a lot of people are treated at not such a good place or maybe not even with a hematologist/oncologist who has a big myeloma practice. And we’re talking about very sophisticated testing. We’re talking about 10 to the 5, 10 to the 6, super sensitive testing. And you’re saying well, what would we do differently?

So, should people watching, Tiffany? If somebody said to you, I live somewhere else in Texas, but I come to MD Anderson—but should the local level, in Lubbock or someplace, should I be lobbying for MRD testing? Tiffany, what do you say? I want to get the doctor’s response, too.

Tiffany Richards:
That’s a good question. It’s also a hard question because, for me, I always go back to, if you have a test, is it going to change what you’re doing? And while MRD status is good to know, I always also go to the flipside. If a patient is told they’re MRD positive, how are they going to feel, after that result. And then, if they’re in a community practice where they’re seeing an oncologist who maybe doesn’t see a lot of myeloma, and now, you have this patient who feels totally deflated because they’re MRD positive.

They go and they look on the internet. And they see, oh, my gosh, my prognosis is worse. And so, what happens, in that scenario? And so, I feel like we shouldn’t leave patients out there who are going to be feeling deflated, without being able to pick them back up and give them hope. And if they’re not in a place where that can occur, then, maybe it’s better not to do the testing. But, again, I think the patient’s situation and having the patient have that discussion with the oncologist is important. But I certain feel like a patient should be able to also have hope, if they do come back MRD positive.

Andrew Schorr:
Doctor, what do you say? Again, you do MRD testing, at certain points, because—and you’re also doing research with your colleagues around the world trying to figure out where does it fit in, and what do you do about it. But that’s not always happening, at the community centers. And they’re not doing that research. So, just for our worldwide audience now, what do you want to say about MRD testing? And I’ll just say for me, and I think, Cherie, you agreed, I want to know, personally.

Cherie Rineker:
Yeah.

Dr. Manasanch:
Most patients, when given the option, they prefer to know. I think, for patients though, one thing that we try to have a community of oncologists and practices. And our own techs actually send their samples here, so we test them here. And it just turned out to be something that was logistically not feasible to do. So, we’ve tried to do this, so that people that cannot come here, their oncologist can send the samples. And the physicians will be happy to do it. But, in terms of our lab, the volume and all of this, it’s just not practical.

So, this is not something that we could achieve. Now, for the community oncologists, community oncologists, usually, they don’t test. They don’t do advanced flow cytometry. So, minimal residual disease testing requires advanced flow cytometry, which is like a new generation where you have some machines that can test many cells, at the same time. You need to have some software that can do that. You need to have someone who is very experienced. If you don’t have a very experienced pathologist reading this test, they’re going to result in tests that are not correct. And that could be an issue.

And so, I think that, if you don’t have the technology to do it, it’s better just not to do it. I think that, when we start changing treatment with this, I think that everyone will open up to it more. I think that it’s very good that the FDA has approved the clonoSEQ test to test for minimal residual disease because I think that’s easy, so the community oncologists can send the samples to Adaptive Biotechnologies.

And they can test us and give our result back. And now, the advantage of—so, that’s, basically, what I would say to these patients. But let me just add something to that. So, basically, if you don’t have it, don’t worry about it. If you really want to have it, and your place doesn’t offer it, you have to go somewhere else because, if where you are, they don’t have it, it’s better that they don’t do it because it’s complicated to get set up. It’s not easy. But now, if you compare flow cytometry to sequencing, so that’s DNA sequencing, DNA sequencing seems to be better.

And so, this clonoSEQ test, the advantage of this test compared to flow cytometry is that, with this test, you can look at different populations of myeloma, within the same patient. So, if you send these tests on diagnosis, they’re going to tell you, okay, 80% of the myeloma has this. And then, the rest, 15 percent, looks like this, and 5 percent looks like this.

And it’s going to tell you that. Whereas the flow cytometry doesn’t tell you that. Now, this test can be done, the sequencing, can be done on almost any patient. Flow cytometry can be done in every patient. So, some patients may not be able to do the sequencing, with the new generation of the sequencing test, the clonoSEQ. Every time, they can read more and more patients. But those are the main limitations. The main limitations of flow cytometry is it cannot inform you on the biology of the myeloma, in terms of how many different myelomas are there, sub myelomas are there in the myeloma.

So, that test cannot inform you of that. But some patients may not be able to do it. Whereas the flow, you can do it in everybody, but it’s not going to tell you about the subpopulations of myeloma. So, those are two tests that are, basically, used for right now.

Andrew Schorr:
I take away as sort of the common man here a couple of things. One is, and we’ve said this on so many of our programs. Cherie, I’m sure you agree. First of all, if you’re living with myeloma, I, personally, think you may want to check in or get a second opinion at a major center, whether it’s MD Anderson or one of the others. And I like the full work up. The other thing that’s going on is the testing continues to advance. So, if I got you right, you’re talking about one person having almost little subsets of myeloma with their own blood, right? Not just one myeloma, but different types. So, it would be super sensitive. Then, the question is what does it all mean differently now that you know. This is like crazy-making. So, it’s kind of like, first of all, have a team that you trust. And recognize, thank God, wouldn’t you say, Cherie, that myeloma patients, in your wonderful example, are on a much longer journey now than ever before You’re such an example of that. And so, this discussion, you’re kind of flowing with your myeloma. Hopefully, it doesn’t come back, but if it does, the testing is going to be more sophisticated. The treatments are going to be more tailored.

Cherie Rineker:
Yes. If I may say, too, when I was first diagnosed, I found out I had multiple myeloma, which I was told was a tradable yet incurable disease, at 44, that’s pretty devastating news. I thought, if I get cancer, you’re going to treat it aggressively. I’m going to go bald for six months or a year, and then, my life goes on. That’s what I thought about cancer. So, to have something that continues on and on is pretty tough to live with. Hopefully, getting to an older age.

And for me, the journey has been both physical healing and emotional healing. And physically, I’ve gotten better and better through the years, now, thankfully, after CAR T especially. But, emotionally, too, that is a lifelong commitment and exercise of trying to stay in the now, trying to stay positive, trying not to have multiple myeloma at the forefront of my thoughts, in everything that I do. And I think MRD negative has played a huge role for me because it has given me some piece of mind that, even if I’m going to relapse, maybe it will be longer. And, hopefully, I’ll stay in remission long enough for another trial to come along for me.

Andrew Schorr:
Yeah. Well, we’ll pray for you exactly that. And I hope so. And I know many of the people watching, and I’ve met a lot of myeloma patients over the years, I’ve been doing these programs since the mid ‘90s.

And, certainly, we’ve lost some people. But so many people are doing better. And there was another treatment waiting for them. And there are others waiting for approval now or close to approval, as we head towards 2019. So, I think learning what’s the right testing, what does it mean, what treatments line up with that, when CAR T, understanding the longevity of that, or who does it work for. And I will just put in a plug for a big meeting coming up. The American Society of Hematology meeting is here in my home county, San Diego. You’ll probably go, Doctor, Tiffany, I’m not sure are you going this year. It would be great to see you.

And so, these studies we’re talking about, trying to answer these questions, it comes out at meetings like that. And there will be a lot of discussion. Who is CAR T right for? What more do we know about MRD testing? When do we do it? What do we do differently because of it? Doctor, did I get it right?

Dr. Manasanch:
Yes, yes, great.

Andrew Schorr:
So, we will be reporting, and my wife Ester and I will be doing some daily wrap ups on the Saturday, Sunday, and Monday of ASH. So, if there’s news about that, we’ll be talking about it. But I think here, we’ve given you a good baseline of where understanding is. So, as we get close to the end here, Tiffany, so people have been listening for 90 minutes. We have a couple of hundred people who have been listening and more. How do people get their head on straight on where this testing and the range of treatment fits better for them? Tiffany, so just help us. Like Cherie was saying, it’s the emotional part of it, with this moving target of myeloma.

Tiffany Richards:
I think I would just tell patients have a discussion with your team about if it’s appropriate for you, at this moment, or if it would be appropriate, in the future. And I think that all of the different response criteria in MRD, I think it’s one of those things that it’s not just going to—they’re not going to be able to really understand it, after just one discussion. I think it’s a continual discussion. And so, I would first say let’s just take it one step at a time. Are you in a very good partial remission? If you are, then, it would be a time to have that conversation about MRD testing or not. If you haven’t gotten to a very good partial remission, let’s just focus on getting you there, rather than looking at the whole entire process, all at the same time.

Andrew Schorr:
Yeah. It’s a lot. And I think, for the family members, often, not Cherie, and not when I was diagnosed with leukemia at 45, that for somebody where, if you’re in your 70s or maybe 80s, and you’re dealing with myeloma, you may have an adult child or a friend helping you make these decisions.

And you feel like you’re kind of drinking from the fire hose, as the treatments have become three, four treatments together, or CAR T, or tandem transplants, or all of these kinds of things, and then, all of the different tests. And the kappa, lambda, and M spike and bands and MRD, it’s a lot to drink in. And you don’t have to feel overwhelmed. How have you—Cherie, would you say knowledge is power? Or having the right healthcare team is part of it? How do you cope when, thank God, there’s more going on in myeloma than ever before?

Cherie Rineker:
Yeah. Knowledge is power, absolutely, a good team that I have at MD Anderson that has been phenomenal, friends’ support.

And knowledge can be a double-edged sword, too. When my last test results came in from MD Anderson, actually, last month, I was so scared to open it because having achieved MRD negativity now, I’m so afraid that the next test is going to show I don’t and that I’ll fall back in that whole thing again. So, like I said, the mental staying mindful and staying positive and just believing in your doctors and your team and knowing that there will be something else on the horizon that can prolong our lives.

Andrew Schorr:
Yeah. And I will tell you, there is a lot going on. But what you know now is you’ve got the little dog that wants your attention. And you’ve got your kids that want your attention. And you’re feeling good today, right?

Cherie Rineker:
Oh, absolutely. Absolutely. I’m beyond grateful. I truly believe that, for me, it was a miracle. I was in a wheelchair last year, and now, I’m out teaching yoga again, incredible.

Andrew Schorr:
Okay. I want to mention that, if you go on the Patient Power site but also on some of you on Facebook groups or whatever, Cherie has written a lot about it. Cherie, what’s the name of your book?

Cherie Rineker:
I have a book, “A Pilgrimage Without End, How Cancer Healed My Broken Heart.” And that kind of ends at when I, in 2016, when I started daratumumab (Darzalex). And I thought that was going to be the end, and I was going to be on that indefinitely. Since, a lot has happened, obviously. So, I’m working on another book now, “Pilgrimage Towards Health, Keeping Hope Alive.” So, I hope sometime in 2019 that will come out. And yeah, now, I’m just advocate and activist and take a lot of questions. Never the doctor questions but more the emotional support that I love to give.

Andrew Schorr:
And raising money for research.

Cherie Rineker:
Yes, I did, for MD Anderson last year, for my 50th birthday, yeah.

Andrew Schorr:
Thank you. Well, we’re so glad that things have worked out. So, doctor, just to wrap up then, this MRD testing that we’ve talked about a lot, along with the other test, is sort of a moving target, right? As is myeloma treatment algorithms, right?

Dr. Manasanch:
Moving target, yes.

Andrew Schorr:
Yes. So, the idea is that patients have the right team. And like you say, you see some patients every month. And it’s an active discussion, right? It’s an iterative discussion.

Dr. Manasanch:
Right.

Andrew Schorr:
So, put it all together though, Doctor. I always like to end this way. Are you hopeful? Because, in the end, what we want to take away as viewers is you’re our barometers. You and Tiffany are our barometers. Knowing what you know, and Tiffany, you said you’ve been doing it 14 years now, right?

Tiffany Richards:
Yeah, 14.

Andrew Schorr:
So, doctor, are you hopeful for those of us who are living with myeloma?

Dr. Manasanch:
Yes, of course. I think that—when I started doing multiple myeloma, all of my patients were doing great. So, this was like 2010, 2011. And it was on clinical trials at NAH with therapy that, at the time, was only given on clinical trials, from the therapy. Everyone was doing great. And I was thinking what is the big deal. Everyone is doing so great. How is this even possible? Like people didn’t used to do well. I think that people have to remember, studies coming out at 2003, the rates of very good partial response and complete remission with therapies, as of 2003, which is 15 years ago, was 10 percent.

And our rate of very good partial response and complete remission right now is, of course, if you do continuous therapy for a year, and most people are in very good partial response or complete remission. So, you went from 10 percent to most patients having it, so now, we’re doing great. I think that we need to figure out why, once we treat it, why it keeps coming back. And I think that’s something that we have not yet figured out yet. And there’s a lot of research trying to find out why. I think that patients will continue to do very well, definitely.

There’s a lot of hope, yeah, definitely. There are so many things that have been going on. There are so many new therapies that are working well. And, again, the self-therapies or the CAR, they’re just the first generation. There are people who are improving on them.

They’re adding things to it. And also, what happens if you give it to someone who has had 10 lines of therapy, but if you give it to someone without a diagnosis? What’s going to happen? We don’t know those things. What if you give it in patients before they develop myeloma? What’s going to happen then? Are you curing them? So, yeah, there are so many things that we can do, right? We don’t have enough—we need more manpower to do all of it. It’s a lot of work. We have a lot of work here, in our department. We have so many things that we want to do. And I think that it’s like the manpower because there’s so much to do.

Andrew Schorr:
Or woman power, there you go.

Dr. Manasanch:
Or women power, but there is so much to do.

Andrew Schorr:
Tiffany, I’m going to let you make the final comment. And that is 14 years there at MD Anderson, right?

Tiffany Richards:
Yep.

Andrew Schorr:
Working in myeloma.

Tiffany Richards:
Yep.

Andrew Schorr:
You’ve seen thousands of patients.

Tiffany Richards:
Yes.

Andrew Schorr:
If somebody comes to you today, obviously, you’ve got to figure out what’s going on. But would you say we can end on a hopeful message?

Tiffany Richards:
Oh, I definitely. So, when I first started 14 years ago, the drugs that were approved that we used—the drugs we had available was bortezomib, thalidomide (Thalomid), transplant, Vad, and melphalan. And that was what we had available to us. And
if you just look at the number of drugs that are now FDA approved for the treatment of myeloma, it’s really remarkable how many options that we have. And every day in clinic, it’s funny because we see these patients every month. And they really do become like part of your family. And I look, and I’ll be like, oh, my gosh, you came right around the same time that I started.
And I’m like oh, my gosh, that was 14 years ago. Wow. And so, there are most definitely reasons to hopeful. And if the
next 14 years are like the last 14 years, then, patients will do really, really well.

Andrew Schorr:
Okay. Amen. All right. I want to thank everybody with us from Houston, Texas today. Cherie Rineker, thank you so much. And all the best to you. Tiffany Richards, thank you. Elisabet Manasanch, thank you so much for being with us. We really explained this in detail. Remember, there will be a replay. And there’s a survey usually we have afterwards. Stay tuned for what we have coming up from ASH. I want to thank the Patient Empowerment Network for pulling all of this together. And I want to thank our financial supporters, Sanofi, Celgene, and AbbVie for supporting the myeloma community. I have a cough I get from a leukemia treatment. In Carlsbad, California, I’m Andrew Schorr. Thank you for joining us. And remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Netowrk (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

ASH 2018 AML Roundtable

Latest Research in AML


AML experts Dr. Sangmin Lee, Assistant Professor Weill Cornell Medicine, Dr. Ellen K. Ritchie, Associate Professor of Clinical Medicine Weill Cornell Medicine, and Dr. Tapan M. Kadia, Associate Professor Department of Leukemia The University of Texas MD Anderson Cancer Center, join this roundtable to discuss all the new drugs to treat AML.


Transcript:

Andrew:

Hello. I’m Andrew Schorr from Patient Power. Welcome to our program, from San Diego and the American Society of Hematology meeting, where the people from around the world discussing the latest in blood related conditions. And there is a lot of discussion given new drug approvals and lots of research in acute myeloid leukemia. And it gives new hope to patients and their families dealing with this acute condition. So, joining me is Esther Schorr. And Esther, you’ve been talking to people. And we have a wonderful panel we’re going to meet, in a second.

 

Esther:

I have. And, especially with the more acute conditions that these wonderful researchers and clinicians are working with, I think that we need to discuss how family members, care partners, caregivers, what active role they need to play in sort of the rapid fire beginning of getting treatment.

 

Andrew:

How you want the best yourself for a loved one. Let’s meet our panel. So, I’m going to have you introduce yourself, so we get your titles right and your institution, please. 

Go right ahead.

 

Dr. Lee:

So, I’m Sangmin Lee from Weill Cornell Medicine. And I’m part of the leukemia program. And I’m an assistant professor there. And I focus on myelodysplastic syndrome and acute myeloid leukemia.

 

Andrew:

Okay. And next to you is a colleague of yours.

 

Dr. Ritchie:

My name is Ellen Ritchie. I’m an associate professor of clinical medicine and the assistant director of the leukemia program at Weill Cornell Medical College. I treat all myeloid malignancies. And I also treat acute lymphoblastic leukemia.

 

Andrew:

Okay. And both, two New Yorkers. And now, let’s go to Texas.

 

Dr. Kadia:

I’m a Texan but a former New Yorker. My name is Tapan Kadia. I’m currently associate professor in the Department of Leukemia at MD Anderson Cancer Center in Houston Texas. My practice is based on research and clinical work in acute myeloid leukemia, MDS. I also look at bone marrow failure syndromes. And I’m glad to be here, so thank you.

 

Dr. Ritchie:

Thank you for having us.

 

Andrew:

So, Dr. Ritchie, I’m going to start with you for a second. So, are we right? It seems like someone’s head can spin, with all of the new drug approvals, and then, also trying to make sense of what’s right for what patient. So, how much have things changed in AML?

 

Dr. Ritchie:

Well, AML used to be a really simple disease because we had two drugs, and that’s how we treated patients. Now, it’s a more complicated disease, partially, because we’re learning a lot more about this disease molecularly. And there are new targeted agents, which have been recently approved, in the last year, for the treatment of AML. Many of them, just recently, in the past few days. Gilteritinib, which is a second FLT3 inhibitor was in there last week. A lot of these drugs are drugs that fall into two categories. Some which target mutations that may be relatively infrequent like IDH1, IDH2, FLT3.

And these are for those specific populations who have those particular mutations.

There are also drugs that are more blanket that cover patients who have really any abnormality, which are added to standard therapy like Venetoclax. Venetoclax was initially approved for the treatment of CLL and has recently had a new label to add to low dose ARA-C or to hypomethylating agents, for the treatment of AML. And that’s an exciting new development where the response rate with hypomethylating agents goes from about 40% to 70%. So, it’s a real advance, for those particular patients.

Also, in the really older and frail population, I always have problems saying it, Glasdegib, which is really a drug, which is directed at the leukemic stem cell together with low dose ARA-C. These have been approved really for patients who are a little bit more frail and older. And it’s a regimen that is more easily tolerated by that age group.

 

Andrew:

So, just a follow up. So, how much of a difference – the FDA approves effective therapies effective therapies, which, hopefully, make people’s life better and longer. So, is that the hope for our viewers watching that whether it’s themselves or an adult parent or grandparents that they can have a better, longer life?

 

Dr. Ritchie:

Well, there are a lot of aspects to leukemic care. It’s not only having a longer life but having a higher quality of life. So, it’s the quality of life that you have, as well as the length of life that you have. So, just to put it in reference, standard induction chemotherapy, where we use two drugs, Daunorubicin and Cytarabine, which my father used to use when he practiced medicine, and those days are – it’s an old combination. But it really requires the patient be in the hospital for 30 days. And these patients are sick. And they require transfusions.

And most of them require antibiotics. And they don’t feel very well, and it’s a difficult time. So, for older patients, are you really willing to spend a month of your life or maybe two months of your life where you really feel terrible in the hospital? That’s not necessarily something that you want to do. So, part of the breakthrough is not just that we may improve overall survival, which we don’t really know, until it’s out in the community, and we see how it works. But whether we can improve the overall quality of life of older patients who have AML. So, and rather than being in hospital, you can have your therapy, in an outpatient setting.

And rather than it being all intravenous, you might have an oral medical that you could take at home, like you do your hypertension pill, really, for your AML. So, these are really important advances because it enhances the quality of life of patients who have acute leukemia.

 

Esther:

Well, and it also sounds like you referenced that a lot of the patients are older with this. And I just can’t imagine what it must be like, if you have two much older people, and one person is, as you mentioned when we were talking earlier, one is out of commission.

The other is not only going to need support from family, but if their partner doesn’t have to be in the hospital to be able to at least be home, there’s some level of support there.

 

Dr. Ritchie:

Right. Well, you guys can chime in. But a typical situation, really, is two older people who are living together where they’re doing just fine as a symbiotic couple. But they both have their illnesses or both have their problems. But once you take one person out of the picture, and that person is very, very sick, it can be very difficult for the other elderly person to actually handle all of the stress of taking care of themselves and all of the stress of taking care of another person. So, one of the key factors, I think, in overall survival and quality of life in patients who are older who have AML is having a caretaker who is reliable for them.

And that may be your child. It may be your sister. It may be a good friend. But there has to be someone in your life, beyond just your spouse, who can be a caretaker for you for a successful therapeutic result.

 

Dr. Lee:

And one thing that is great about the medicines that are coming out are that they’re very well tolerated, especially the IDH drugs and Venetoclax. They’re very well tolerated. You can do it outpatient. So, for a lot of older patients, as you know, if you stay in the hospital more, you’re exposed to infections. Your performance status may decline. So, patients actually do better with an outpatient therapy. I think that’s beneficial

 

Esther:

And also older people. I have two aging parents, thank goodness doing well. But they’re in their 80s. And just driving to the clinic is a big event. But if you’re having to do that every day for treatment or going to visit.

 

Dr. Ritchie:

Right. And we don’t want sick people driving necessarily to our clinic because, if your hemoglobin is 7, and your platelets are low, you’re not in the best situation to be reactive to the problems of traffic and cars.

So, transportation is also a real issue, I think, when patients are older and coming in for treatment.

 

Andrew:

Dr. Kadia, so we’ve mentioned a couple of these cancer genes. IDH, FLT3, I think. So, these are oncogenes, right?

 

Dr. Kadia:

Right. So, what’s been great, and I think this has been greatly summarized by my colleagues, but we’ve had sort of a revolution in how we treat AML and many cancers, but particularly AML and the liquid tumors. With the advent of what we call next generation sequencing, we’re able to really get the mutations and the data from the leukemia cells. We find that there are recurrent mutations. Mutations are changes in the DNA that happen over and over and over again, in different people with leukemia. So, it made us realize that, if these mutations keep happening in AML, they must drive the AML.

There must be something about them that makes the AML happen. And, in fact, that’s the case. So, in a handful of those mutations, things that people have really studied, we now know that things like FLT3 or “flit 3” is a mutation that really drives proliferative AML. And so, people said, well, if that drives it, can we develop a drug target inhibitor of that mutation to shut the leukemia down? And indeed we can. We used to use a drug call Sorafenib last year, over a year ago. A drug called Midostaurin was approved with chemotherapy in the front line. And just recently, as was describe, just a week ago, Gilteritinib was approved in patients who have the FLT3 mutation, but they’ve had relapsed disease.

So, that’s just one example. The second you said IDH, right, isocitrate dehydrogenase, another mutation. We didn’t know what it meant. But people worked and worked and figured it out. And they found out there’s two mutations, an IDH1 and an IDH2 mutation. Each of those drives that particular subset of leukemia. And it turns out you can make inhibitors to each of those, and they work. An oral medication you take once a day for people with relapsed disease actually works.

And it doesn’t work like regular chemotherapy. We describe intensive chemotherapy. You put them in the hospital, their hair falls out. They have mouth sores and diarrhea and nausea and vomiting. We don’t see that, with these pills. We do see some side effects. And, certainly, the patient and the family member need to recognize those side effects. So, there are side effects. But they’re different. They’re more tolerable. They’re more manageable. And so, that’s what we’ve been able to do, get people home, take these medications, and target these specific mutations.

So, among the many mutations we’ve discovered, we found drugs for probably two to three of those targets. But we also found that some of these mutations will predict for responses to other drugs like Venetoclax.

 

Andrew:

Let’s talk about testing. How do you know?

 

Esther:

I was just going to say it really sounds like you have to be tested.

 

Dr. Lee:

Yes.

 

Esther:

To know where you fall.

 

Dr. Ritchie:

And I think that’s one of the big barriers right now that I feel the insurance industry has not really caught up to what it is that we’re doing in AML. So, every patient who is getting or has a suspicion that patient has AML, that patient, when they have a bone marrow biopsy and they see a doctor should have a next generation sequencing sent.

The problem is this costs thousands of dollars. Now, some insurance companies are not – they don’t really care or aren’t really cognizant of the quality of the different NGS panels. And they make deals to cover with one or not cover at all. So, it can be a hassle for the patient. And it can be thousands of dollars expense. So, that’s something that I think the whole industry is working on to try and enlighten insurance companies and to make them pay for this particular sequencing. MD Anderson has their own in house. And you probably have worked out a deal with insurance companies.

 

Dr. Kadia:

No, we have. So, I think more and more, insurance companies are beginning to realize that this is a part of the disease treatment. If you have pneumonia, you’re going to get a chest x-ray. If you have AML, it’s becoming standard.

It has for years. We do FLT3 mutations. We do something called NPM1 mutations. For years, we’ve been doing this in AML. Now, what they need to realize is that we need to expand that to what we call a sequencing panel, which are 80 different genes, which are commonly mutated. Why? Not just because we’re interested and we’re curious, but because these mutations play an important role in telling the patient this is your prognosis. And this is the drug that we’re going to treat it with.

 

Dr. Ritchie:

Or even, if this patient – and just because you’re older doesn’t mean you’re not a candidate to be a bone marrow transplant candidate, there are some mutations that we find that really propel us to wanting to have that patient –

 

Andrew:

It’s all about getting what’s right for you or your loved one. So, let’s back up for a second, Dr. Lee, just so we understand AML. So, first of all, how old is the typical patient? What are the symptoms that present? For somebody who is watching us, maybe somebody said this could be AML.

 So, what is AML? And how does it typically show up and for who?

 

Dr. Lee:

So, AML stands for acute myeloid leukemia. So, in your bone marrow, bone marrow’s job is to make blood cells, including your white blood cell, which is your immune system, hemoglobin, which are the red cells, and platelets. And they all are manufactured in the bone marrow. So, what we’re talking about here is that, basically, the factory, the stem cells that make the blood cells, have gone wrong, basically. And there are abnormal myeloid stem cells that proliferate. And your bone marrow is full of these abnormal stem cells that are not able to make normal kinds of immune system and hemoglobin and platelets.

So, it’s an acute leukemia meaning that, sometimes, people are doing – a lot of times, people are doing well. And then, all of a sudden, their bone marrow develops a leukemia. And all of a sudden, you become symptomatic.

So, symptomatic means that, if your bone marrow is not making red cells or platelets, you might be more tired. You might see some easy bruising or see these little dots pop up on your skin.

 

Andrew:

Petechiae.

 

Dr. Lee:

Petechiae in your skin. Or you might have an infection that doesn’t go away because your immune system is affected. So, there are various ways that people are diagnosed, based on how they feel. Sometimes, people just get a routine blood work by the primary physician, and they are just discovered to have leukemia, even though they don’t have symptoms. So, it kind of varies.

 

Esther:

But there’s different paths with leukemia, obviously, that there’s AML, which is do not pass go, something needs to happen right now. And some of the more chronic forms where you have a little more time to kind of figure out what’s going on.

 

Dr. Lee:

And a lot of times, you can differentiate because, if you see a primary care physician or Emergency Room, they can actually look at the blood cells and do what’s called a manual differential.

Basically, some person looks at the blood cells under a microscope, and you are able to see abnormal leukemic looking cells that you wouldn’t see in any other condition. So, that’s how you know that you have leukemia.

 

Andrew:

So, a family is saying, okay, did we do something, did the patient do something, did something happen to them that caused this. So, you sort of fall off of this leukemia cliff into this acute I call five alarm fire situation.

 

Dr. Kadia:

No, you’re absolutely right. And I completely agree with that. Leukemia, at least AML, acute leukemia, is a very rapidly progressing disease, in most cases. And it’s, usually, a medical urgency, if not a medical emergency, like you said. Most of the time, no one has done anything to cause leukemia. And many people are doing fine, until they actually have the diagnosis, and they get very, very sick very rapidly. Patients tell me all of the time, I was just traveling. I was on a cruise. I was playing golf. I felt fine. Why do I have AML? It comes on very acutely, hence the name acute, so very quickly.

The risk factors for AML, first, is age. The older you are, the higher the risk of developing AML. The average of developing AML is around 68 years of age. We know that there are younger people who get AML as well. But we know that that AML is a little bit different than people who have older AML. The younger AML’s tend to be more rapidly proliferative. They have high white counts. The older AML is often associated with a disease called myelodysplastic syndrome, which is related. So, they have low counts, feeling kind of icky. Their counts are not great. And then, they develop this surge.

And so, age is certainly a risk factor. Prior exposure to chemotherapy or radiation for another cancer predisposes you to AML. If you are exposed to things like benzine or if you’re a heavy smoker that can sometimes predispose people to AML. But, certainly, it’s not anyone’s fault. And no one knows. And why couldn’t I have detected this earlier? Nine times out of ten, you could not have detected it earlier. It happened two weeks, three weeks prior to what just happened.

 

Esther:

And is the treatment for a younger patient different than for an older patient?

 

Dr. Kadia:

It can be. It can be. And often, what we look at, and age is not the only thing. We don’t look at age as a number but more of a fit and unfit person. So, if an older patient, they tend to have more comorbidities, history of hypertension, diabetes, heart disease just because they’ve lived longer. They have 60, 70-year-old organs. And they may not be as fit as a 25, 30, 40-year-old. And so, then, you base your treatment paradigm on whether you think they can tolerate some intensive chemotherapy versus not.

But a point that I wanted to expand on, when you present in the Emergency Room with acute leukemia, it’s a rare folks, 19,000 cases a year, compared to something like breast cancer or lung cancer, which is very, very common. And so, typically, someone will come to the Emergency Room. They’ll be seen by the Emergency Room. They’ll consult the local hematologist oncologist. They’ll come to see that patient. Or they may know a local hematologist oncologist.

While community physicians can treat the disease, sometimes, in the acute setting, and for reasons we described earlier, it’s nice to go to an academic center or larger center who can do some of the initial work up, the mutation screening, it will be easier.

Maybe not have problems with getting the insurance. Get the diagnosis right. Get the pre-treatment data right, so that you can really formulate a treatment plan. And once that treatment plan is in place, then, you can decide can I get some of this treatment here, can I go back to my local doctor?

 

Andrew:

Well, I think that’s really critical. So, you are both in really big cities. Our largest, New York, Houston. And there are choices of what hospital you go to or what clinic you go to. Some may be in a more suburban or rural area. But it seems like, if this is suspected, if you can get with this changing landscape, at least a consultation or even your community doctor calling one of these folks to have a plan, an architect plan, even if the community doctor is sort of the general contractor, if you will. But there’s a lot –

 

Dr. Ritchie:

But I want to say something about that a little bit.

 

Andrew:

Sure, please.

 

Dr. Ritchie:

These are all very new drugs. And leukemia patients need a lot of care.

And we don’t really know what we need to know about a drug, until a drug is approved, and it’s being used widely. So, it is something that community doctors should confer with people who have used the drugs. And probably the most impressive abstract that I have seen at ASH this week involves really our ability to develop these sorts of drugs where there was an abstract looking at patients who had FLT3 mutations and how many leukemia patients we have every year in the United States who have FLT3 mutations. Looking at the number of trials that we have open for FLT3 inhibitors and now combinations of FLT3 inhibitors with some of these other drugs.

And looking as to whether or not we have enough patients. It’s very sad, in this country, that only five percent of adults are participating in clinical trials.

So, the ability of our leukemic world to develop drugs that are actually going to improve the quality of life and improve the treatment of these diseases has depended on that very generous five percent of the adult population who is enrolled on clinical trials. This contrasts greatly with children. The Children’s Oncology Group manages to enroll about 50% of children in this country on Children’s Oncology Group studies. And the overall survival of children, in every single malignancy where the COG trials are open are superior to adults’ overall survival.

So, now that we have these drugs, we want to hone in and find ways to make these drugs even more effective. The IDH2 inhibitors are about 40% effective CRs. But it would be nice, if we could figure out a way to combine it with something else and make it 80%.

 

Andrew:

CR, complete remission.

 

Dr. Ritchie:

To make it 80% effective. And the way we are going to do that is by enrolling people on clinical trials.

 

Esther:

But it sounds like the onus is really on patient and their care partners to say hey, if I’m in a rural setting, and I’m not near one of these major centers that I want to have a consultation. I want you, doctor, in my city, and consider a trial. It’s a big responsibility.

 

Dr. Kadia:

Absolutely. I think you have to be an advocate for yourself. And I’ve seen patients, when they’re first diagnosed, their head is spinning. It’s a scary, scary thing. You Google AML, and it’s not a fun thing to read.

 

Esther:

No.

 

Dr. Kadia:

So, their heads are spinning. So, this is a really good time for the family, the caregiver, the friend to come and support that patient and say, look, I got you. I’ll go with you to the doctor’s appointment, and I will advocate on your behalf. And you will advocate on your behalf to say, look, you’re my doctor. You’ve been my dad’s doctor.

 You’ve been my cousin’s doctor, and I love you. But I think that I really want to get a specialty opinion from a disease specialist who treats this really, really rare disease that happens to be really aggressive. And where there’s been so much development, just in the last two to three years where things that we used to do before, we don’t do anymore. It’s just not the case. And people get afraid of clinical trials. Well, I don’t want to be a guinea pig. But it’s not necessarily a guinea pig. I think, you can really ask the doctor that you’re seeing what does this clinical trial entail. Am I going to get a placebo?

Am I going to get standard treatment? And what you’ll see, as far as I know, is many of the trials, most of the trials in AML and leukemia these days, are full treatment trials where they’re studying potential combinations and things like that. And really, get to know your risks, before you sign the consent.

 

Andrew:

You referred to people Googling it and whatever. So, Dr. Lee, given what you know and what you’ve been hearing at this meeting like at the convention center next door, would you say that this is changing so much that, probably, what you’d see in a general write up from last year or the year before on AML, is out of date?

 

Dr. Ritchie:

Then, maybe don’t Google.

 

Dr. Lee:

Absolutely. I think Google is very dangerous because a lot of times, your information is based on how updated it is. So, if you have so many drugs that are approved, and whatever you look up is not updated, according to that, then, it’s very outdated. So, I think Google can be very dangerous.

 

Esther:

So, what should a patient do? So, God forbid, something happened with AML, in our family, Andrew or somebody else. What’s the first thing that family should do, in terms of trying to get enough information?

 

Dr. Lee:

I think, for AML, what’s very important to know is that there are two general behaviors of AML. One is something that needs to be treated right away, as in the same day. Typically, those kinds of patients have a very high white blood cell count, and they’re more symptomatic. So, in those cases, I would advocate that you do not have a lot of time to shop around.

So, if you are really far away, you need to do what you can to treat the disease first. Assuming you’re pretty stable, if your blood counts are not proliferative and changing, you do have time to ask for an opinion. And I would, like anything else in medicine, I would go to a person who treats a lot of the condition. AML is not a common disease. And treating an AML patient requires not only giving drugs but a lot of supportive care. So, you need to go to someone who sees more AML patients. So, that’s what the patient needs to advocate.

So, the first question the patient should probably ask a doctor is how many patients of AML have you treated. And is there someone who you know who has expertise in treating AML? And given the acute nature of things, for us, when patients call, we often squeeze them in same day.

Unlike other kinds of cancers that move slowly, we often see patients on a very short notice because it’s an acute leukemia.

 

Andrew:

Decisions have to be made fast. So, we’ve talked a lot about the family role, whether it’s somebody your same age, and you’re an older person, or the adult child, you can play role the terror, as you referred to, that comes with the diagnosis. So, it sounds like it’s important to sort of pick yourself off the floor, identify a team or consulting healthcare team members who have expertise in the field, to make sense of this IDH and FLT3 and all of the different stuff, and, hopefully, have insurance support, so you can get the testing that’s right for you.

Now, with all of these different drugs, if you find that one is not working or no longer working, with this whole array of treatments, is there something else that probably you can switch to, Dr. Kadia?

 In other words, you’re not out of choices.

 

Dr. Kadia:

No, you’re not. And one of the great things about having these trials and having these new drugs approved is now, we have so much more in our toolbox than we used. Before, like we said earlier, we had two drugs. We had a anthracycline and cytarabine, there’s two types of drugs. And we just used those. We combined it with other things. But it was really the same kind of backbone. But now, you have IDH inhibitors. You have FLT3 inhibitors. You have this drug, Venetoclax, which has shown remarkable response rates, with a low intensity chemotherapy that’s tolerable to people who are 60, 70, 80 years of age.

And so, even if you did not respond, or if you responded and relapsed after your first AML treatment, there’s not a significant loss of hope. You say no, there are other things available. There are many drugs in development. There are many clinical trials. And very often, some of the best care you receive is on a clinical trial because you’ll have a research team and research nurse, in addition to your doctor, who is constantly monitoring, following every single side effect that you have, trying to address every question you have because it is regulated very closely.

So, there are many options. And, certainly, many of the academic centers and even certain other organizations now are offering these trials.

 

Dr. Lee:

One thing that is extremely important for patients to realize, actually, for clinical studies, is that each individual patient is not a statistic. So, let’s say a drug only has 20 or 30% response rate. You don’t actually know, a lot of times, if you’re going to respond or not until you take the medicine. But if you happen to fall under that 20 or 30% that works, it doesn’t matter what that success rate is. But you have to make the steps to try. And that’s what’s the most important thing about treating AML patients.

 

Dr. Ritchie:

I want to mention a couple of other drugs, which have been approved that we haven’t talked about. One is Vyxeos, which is a drug, which is the anthracycline or cytarabine, and Daunorubicin that’s enclosed in a fat globule.

 

[00:36:05]

 

And it’s given differently. It can be given twice a week, for example, or three times a week, depending on what the decision is of the clinician. And it can be given on an outpatient basis. You usually do have to come into the hospital, at some point in time. But unlike normal 3+7 chemotherapy, you may even keep your hair with this. But that’s an option for someone who fails some of the upfront drugs, potentially, or has myelodysplastic syndrome, which is a type of pre-leukemia that develops into acute leukemia.

And it looks like, in these pre-leukemia patients who develop acute leukemia who have myelodysplastic syndrome, it may be a very effective drug. We also have, back in the tool box, Gemtuzumab, Ozogamicin, which is also known as Mylotarg, which was a drug originally approved for older patients who fail standard chemotherapy.

 And it’s an antibody, which binds to an antigen on the leukemia cell called CD33. And it’s connected to an antibiotic called Calicheamicin, which can be enclosed into the leukemia cell and kill the cell. This drug was taken off the market for a period of time because of certain liver abnormalities and has been brought back onto the market. The dosing schedule has changed somewhat. But it’s another option. And it’s an immunotherapy option, which we can use for patients who may fail original therapy.

We also are combining it, in younger patients, with standard chemotherapy who may have a better sort of favorable karyotype or their chromosomes have a more favorable response to chemotherapy that we combine that antibody with regular chemotherapy for a better outcome.

 So, the tool box is really expanded. And I think we’ve talked now about all of the agents.

 

Andrew:

We’ve left one area out though, and that is transplant. So, first of all, I’m living with myelofibrosis and know that there’s a percentage of people who progress to secondary AML. And before, you didn’t have much for us, maybe transplant. And also, other primary AML people who would go to transplant. So, where does transplant fit in, whether it’s primary AML or secondary AML or other drugs for secondary AML? Why don’t you take the transplant first? Where does it fit in?

 

Dr. Ritchie:

Well, we look at a lot of things, when we look at an AML patient. We’re looking at their age and their fitness, what their comorbid illnesses are. We look at their disease. We look and see what are the chromosomal abnormalities that we see, in this particular leukemia.

 And we group them according to favorable risk, people that might respond well to chemotherapy alone, people with intermediate risk where they may or may not have a good response to conventional chemotherapies, and poor risk. We are now also doing the molecular testing. So, we do that 50 gene or 80 gene test where we see what mutations there are, in the person’s leukemia. And we put all of that information together to see what we think the prognosis of the patient is.

So, if the patient has already had heart failure and has had bypass surgery, and they have diabetes that’s not on good control, and they have an unfavorable AML that we would transplant, we may not refer that patient to a transplant consultation because we don’t think that they’re strong enough or fit enough to get through a transplant.

 But my 79-year-old tennis player who has been playing tennis every single day, and the only comorbid illness is hypothyroidism, and they have an unfavorable mutational panel or an unfavorable chromosomal karyotype, then, that patient I would refer to a transplant consultation for cure.

 

Andrew:

Okay. And then, secondary AML where my understanding is some of these drugs may help someone like me, if I progressed, from myelofibrosis. I don’t know whether –

 

Dr. Ritchie:

Secondary AML, if you were a fit person, I think most of us would send you for a transplant consultation.

 

Dr. Kadia:

I think the bottom line is we look at two things. We look at the risk of the leukemia and the risk for the patient. So, we look at the disease and the patient. If the disease is high risk or even intermediate to high risk, we consider them candidates for transplant. Then, the next step is fine, we think you should get a transplant.

Would you do well with a transplant? Is the morbidity and mortality rate going to be high, in your case, or is it going to be low? If it’s going to be high or even intermediate to high, then, we can’t do a transplant. We shouldn’t do a transplant, unless we mitigate some of those factors. If the risk is low, then, that patient should try to get a transplant. Then, there’s the whole thing of do we have a donor available. A donor is, typically, a sibling who is a match. We also have national marrow donor program, which you can get an unrelated match. Occasionally, we do something called a haploidentical where you can get a son or daughter or mother or father to be a match.

Those are probably less likely in older patients because they’re a little bit tougher. And we do those more in younger patients. But there are many options for transplant. I don’t think it’s off the table.

 

Dr. Lee:

One thing to be very clear about transplant is that it’s usually an option, once you get rid of the disease. So, it’s not something you go into, when you are first diagnosed.

 

Andrew:

You’re going to knock it back with the drugs we’ve been talking about.

 

Dr. Lee:

Correct. So, transplant is a modality to really keep the disease from recurring.

So, one thing that is very important that is coming out these days, with ASH and other meetings, is importance of how we measure disease, after treatment, before we go to transplant. And increasingly, there’s a way we’re getting more sophisticated into measuring how much disease you have left over, after induction therapy. And it’s called measurable residual disease, MRD. And you can go deeper and deeper and look, and there’s actually data showing that less disease you have, or if you don’t have any disease, you better after transplant. So, one important thing the patients should remember is that it’s very important to try to eradicate your disease, before you go proceed to transplant.

 

Andrew:

Let me see if I’ve got this right then. So, if you can, you’re going to do this testing to see what version of AML do you have, by these panels of genomic testing.

 

 

Dr. Ritchie:

And the karyotype, the chromosomes that are inside of your leukemia cells.

 

Andrew:

Chromosomes, okay. And then, you’re going to see are there drugs that line up with that that can knock it down to minimal measurable disease? Are you a candidate for transplant that can take it further and maybe give you a longer life? Is there a donor? But for people who are not candidates for transplant, Dr. Ritchie, are we just saying there’s not as much hope for them?

 

Dr. Ritchie:

I like to tell my patients that there is always hope. The issue will be, for these patients, that they will, eventually, need to enroll in clinical trials of new drugs and new combinations, to try and keep their leukemia in remission or to treat a relapse of their leukemia. Although we have all of these new combinations, one of the things that we haven’t really established is, when you fail one of these, and you have a relapse of your disease, what is the next best step?

We don’t really know it for any of these drugs. So, clinical trials become very, very important and really the key to a longer life for those people who are not transplant candidates.

 

Andrew:

That’s for ASH –

 

Dr. Lee:

I definitely agree with Dr. Ritchie. I have one example. I have a patient in her mid-80s. She was diagnosed more than three years ago. And she had a very aggressive leukemia that did not respond to the Decitabine. And she was actually very sick and had a lot of heart issues. She happened to have an IDH2 mutation, and we had a trial. So, we gave her the drug. And more than three years later, she’s still taking the drug, has a completely normal blood count, and going about her business. And she remains in remission and ongoing.

So, back then, we didn’t know how good the drug would be, of course. And we had a clinical study, and she enrolled. And you don’t know, when you have clinical study, how well it’s going to work. So, it’s very important to keep an open mind and be proactive about it.

 

Esther:

If one relapses with AML, in that scenario, do they need to be then retested to the –

 

Dr. Ritchie:

Yes.

 

Esther:

Because I know, in some of the other leukemias, that’s the case.

 

Dr. Ritchie:

The NCCN guidelines really recommend that there is a mutational panel done at diagnosis. But if we’re going to send someone to transplant, there’s a lot of sort of disagreement about how you measure minimal residual disease. But one of the things I think most people are beginning to have a consensus about is repeating the molecular panel to see whether or not we still see those molecular abnormalities, in addition to other things.

 

Andrew:

It’s the driver gene.

 

Dr. Kadia:

Exactly.

So, I think, what we realize is that this is a disease that’s constantly evolving. So, we hit it with chemotherapy. It evolves to progress. We hit it again with something else, it evolves. So, the evolution happens either through chromosome abnormalities or to mutations. So, it’s important to recheck some of these mutations to see now, hey, they didn’t have the FLT3 before, but now they do. Now, we can target it with something else.

 

Esther:

It’s kind of wily, isn’t it?

 

Dr. Kadia:

Exactly. It just continues to –

 

Andrew:

So, I just want to ask you, just poll you really quickly. So, for our patients and family members who are watching, you’re their barometer on how things are changing in AML and what it could mean for themselves or loved one. Are you especially hopeful now?

 

Dr. Kadia:

I am hopeful. I am optimistic. I’m excited. I think these are great times at AML. We talk about the new drugs that have been up front for patients who are in upfront setting, people who have relapse disease. There’s hope for them. We talked about what do you do if you’re not a candidate for transplant. We’re looking now at things called maintenance therapy where we give induction, we give consolidation.

We can give you something that’s low intensity for a very long period of time to maintain the remission and not let you relapse because, sometimes, when you relapse, you say now, we’re kind of behind the eight ball. But what if we just don’t let you relapse? We give you a maintenance therapy. So, these are trials that we’re doing. I think they’re exciting times. I’m very hopeful and excited.

 

Andrew:

You’re positive. You two?

 

Dr. Ritchie:

I feel that I’m living in a period of a revolution. And I think it’s not just a revolution in acute leukemia. It’s going to be a revolution in all of medicine that, as we learn about these mutations in the blood, we learn things about not only treating acute leukemia but maybe even about other medical conditions. I’m going to give you an example of that. We have learned that patients who have certain of these mutations, if they don’t have acute leukemia and have myelodysplastic syndrome, some of these mutations make for a higher risk of cardiovascular disease.

 So, that, as a physician, I now am really worried about the cardiovascular risk factors of my patients who fall into that category, in addition to their disease. They’re also finding that some of the mutations that we are finding in blood diseases, they’re finding in the brain. So, some of the drugs that we are using for hematologic cancers may be useful for pretty terrible cancer in the brain called glioblastoma. So, as we start to make these kinds of connections, this is revolutionary. This is unbelievable.

 

Esther:

Well, it’s forcing a more holistic approach, too.

 

Dr. Ritchie:

We’re filling in little pieces of the one million piece jigsaw puzzle that really confers the health of a human.

 

Andrew:

And you grew up with it, right? Your father is a physician?

 

Dr. Ritchie:

My father and my grandfather and my brother are all physicians. My grandfather was the first pediatrician in the state of Iowa.

 

Esther:

Wow. That’s quite a legacy.

 

Andrew:

How about you, Dr. Lee?

 

Dr. Lee:

I’m very excited, and I’m very optimistic. We have spent a lot of time talking about mutations. But one area that is emerging and, hopefully, in the next [Crosstalk] few years, that will be powerful in AML is, of course, immunotherapy. The immunotherapy has transformed solid tumors. Every solid tumor, there is some sort of immunotherapy. And we’re not there yet, but there’s a lot of clinical studies looking at how to harness your immune system into treating leukemia. So, we haven’t even hit that yet. But a few years from now, I’m sure there will be new immunity therapies that will be very relevant in leukemia. So, it’s very exciting.

 

Andrew:

So, for the family members –

 

Esther:

We just have to be hopeful and stay on top of it.

 

Andrew:

But I think connect with the specialist. You have your community doctor, if you haven’t gone to the big, academic medical center, with their specialists in this field. Make that connection because you hear the change.

 You hear the need for testing to know what is your specific situation that you’re dealing with. Or if you are coming out of a remission, do you need to be tested again? Yes, to know what’s going on then. What are your options? But thank you so much to our panel. It’s been a great discussion. And thank you for helping, in the research you do, because you’re helping lead the way. And if that helps with brain cancer and some of these other areas, put the pieces of the puzzle together, Dr. Ritchie, as you said, for you’ll be very pleased. And your father and your grandfather and all of your medical people in your family will be so pleased.

Esther, I’m really delighted that we can tell this story. Serious illness, acute illness, but there’s stuff to talk about with your healthcare team. Thank you for watching. We wish you and your family the best. And remember, from Esther Schorr and Andrew Schorr –

 

Esther:

Knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.


We thank Daiichi Sankyo and Jazz Pharmaceuticals  for their support.

Ask the CLL Expert – Dr. Richard Furman

Ask the CLL Expert – Dr. Richard Furman

CLL specialist Dr. Richard Furman, Director of the CLL Research Center at Weill Cornell Medicine, answered patients burning questions live in this installment of Ask The Expert.


Transcript

 

Andrew Schorr:

And hello.  Greetings.  I’m Andrew Schorr in southern California, San Diego area, and I’ve been living with CLL for 22 years, so I’m vitally interested in today’s Ask the Expert session, this Patient Empowerment Network program.  We want to thank PEN, as we call it, and also the financial supporters of this program, AbbVie Incorporated and Pharmacyclics, although reminding you that they have no editorial control.  You’ll be hearing from our leading expert in CLL in just a minute.

Over the next 30 minutes or so we’ll get to as many questions as we can.  Remember not to make it too personal.  Let it help everybody in the community.  And also discuss what you learn with your own CLL provider so you get the treatment that’s right for you.  Okay.

Let’s meet our expert joining us from New York City and Weill Cornell medicine, and that’s Dr. Richard Furman, who is the director of the CLL research center in New York City at Weill Cornell.  Dr. Furman, welcome back.  Thanks for being with us.

 

Dr. Furman:

Thank you.  It’s my pleasure.  Thank you for having me.

 

Andrew Schorr:

Okay.  We have lots of questions.  One of them that somebody wants to know about is, first of all, if they’ve been‑‑maybe this is an easy one.  If they’ve been diagnosed with SLL, small lymphocytic lymphoma, is that the same as CLL and what we’re talking about with CLL applies to them?

 

Dr. Furman:

So that’s a very important question, and this is one that I actually think is very indicative of how little we used to know.  So in 1993 we actually had a diagnosis of CLL, chronic lymphocytic leukemia, and a diagnosis of small lymphocytic lymphoma.  And we had patients that were diagnosed with SLL if they had a lymph node sent to the pathologist, or they were diagnosed with CLL if they had a bone marrow biopsy sent to the pathologist.

Clearly, we knew that patients could only have one diagnosis and not two, so in 1994 with the new lymphoma classification system the term was actually changed to be CLL/SLL.  So they really are exactly the same entity.  We don’t actually refer to differences anymore, and the whole, the whole individual‑‑the whole disease should be called CLL/SLL.

Now, an important thing is sometimes people require having a lymphocytosis to meet the definition of CLL, but the truth is both conditions are exactly the same.  Both should be treated exactly the same, and there should be no difference based upon having a lymphocytosis.

 

Andrew Schorr:

Okay.

 

Dr. Furman:

Why this is most important, let me just add, is that there are sometimes people will be diagnosed with stage IV SLL and it’s very important to recognize that these stage IV SLL patients unless they have thrombocytopenia below 100,000 like the Rai stage would indicate really are not stage IV.  So the lymphoma staging system would automatically make them stage IV, and that’s certainly not correct.

 

Andrew Schorr:

Okay.  Good point.  All right.  Here’s a question we got in from Julia and Betty and Shelly and Mark.  They all asked a similar question.  They’ve been on Imbruvica for five years now with success.

Is it working for most people, and what are some reasons why it doesn’t work for everyone?  And then what treatment options do you recommend if they relapse on Imbruvica?

 

Dr. Furman:

So right now I think the most important, there are a lot of prognostic markers available for CLL.  At last count we’re probably up to 115.  What’s most important is in 2018 what are those prognostic markers that really are relevant to the patient, and really as long as you stay as CLL you’re going to be able to have your disease very nicely controlled with our current agents and our novel agents.

So there are certain things that do indicate patients are likely to progress on ibrutinib, not likely progress must but who may progress, and people who might need something more, and that’s where a lot of our current clinical are research is focused.  So patients who have a risk of developing a Richter’s transformation or patients who have a likelihood of developing a BTK mutation that might generate resistance to ibrutinib are the two groups of people that we worry about most.

17p deletion is probably the most important predictor for predicting those patient outcomes.  There are other things that are predictive as well like having a NOTCH mutation.  Those are all readily obtainable prognostic markers that allow us to determine who’s at risk and who’s not at risk for progressing on ibrutinib.  If you don’t have 17p deletion or NOTCH1 mutation you have almost a 99 percent chance of being free from progression at five years on ibrutinib.  And it looks like most of the people who are going to progress will progress within five years.  So I think making it to that five‑year mark is really very‑‑is the most important thing.

 

Andrew Schorr:

Okay.  So if you do progress, what then?

 

Dr. Furman:

So fortunately we have a lot of great agents.

Venetoclax works very effectively in patients who progress on ibrutinib, generates some very, very deep responses and very long‑lasting responses.  So that’s certainly one option.  Another option is to be treated with a PI3‑kinase inhibitor.  So we have idelalisib and duvelisib now approved.  We will shortly have umbralisib approved as well as a novel agent.  We also have a whole array of other agents coming down the pipeline looking specifically at means for progression on venetoclax.  So we have an MCL1 inhibitor which targets the protein that’s likely responsible for resistance to venetoclax.  So all these things are actually currently in clinical trials and certainly will hold a great deal of promise.

 

Andrew Schorr:

Okay.  Here’s a question we got in from Jeff.  He says, for young and fit patients with relapsed disease what are the best combos now and coming.  And I suspect maybe Jeff had received FCR, so if he relapses after FCR, what about that?

 

Dr. Furman:

So my belief is that these novel agents should always be used up front, or if you’ve gotten chemotherapy up front they should be used immediately at relapse.  A lot of patients and physicians have the idea that there’s a benefit to holding back until you really need something, but I believe putting our best foot forward first is always the best approach.  So I always recommend going forward first with BTK inhibitor therapy, followed by venetoclax or venetoclax followed by BTK inhibitor therapy.  And I think so in a patient who has relapsed after FCR it will be ibrutinib or acalabrutinib.  In a patient who has relapsed after acalabrutinib and ibrutinib would then move on to venetoclax.

Now, what I’m really very excited about is the possibility of the combination of either BTK inhibitor therapy plus venetoclax or PI3 kinase inhibitor therapy with venetoclax.

You know, both of these combinations really take advantage of the synergy that happens when you take a BCR antagonist like ibrutinib, acalabrutinib or idelalisib and duvelisib and combine it with a Bcl‑2 inhibitor.  And it really sort of enables us to get very, very deep remissions with actually as short as just 12 months of treatment.  And so those are what we’re currently testing in patients right now and what I hope will be the frontline treatment for patients in the not‑too‑distant future.

 

Andrew Schorr:

Now, one of the things people wonder about is if you take these big guns and put them together could you, like you’ve been able to do with FCR, stop treatment or take a break from treatment at some time.

 

Dr. Furman:

So I’m a big believer in that if something’s working and you’re tolerating it well that we shouldn’t mess with it, but we are currently studying two different processes with relationship to the ibrutinib plus venetoclax combination.  So we’re taking patients who become MRD negative on the combination after 12 months and randomizing them to either just get ibrutinib or to get placebo.  And so that’s going to give us information as to whether or not it’s safe to stop patients on the combination and treat them with nothing long term.  We’ll see, one, how many patients relapse, and hopefully none, and, two, if they do relapse whether or not we can then restart ibrutinib and control their disease.  So this will provide us that important question as to whether or not we’re giving up something by discontinuing the therapy.

We’ll have as our comparative those patients who got ibrutinib plus venetoclax for 12 months and then just remained on the ibrutinib.

And so that will sort of be the patients who will continue on with their therapy, and then the other half will be patients who have discontinued all their therapy.

My belief for going to venetoclax is that you’re going to get almost all of the bang for your buck out of the first 12 to 24 months, so continuing it is unlikely to yield an additional benefit, so I think stopping it is safe.  But, once again, these are the studies that will provide us with those data.

 

Andrew Schorr:

Okay.  Now Maureen sent in a question where they responded to venetoclax and rituximab and they wondered what about testing for minimal residual disease?  They don’t have any lymph nodes or anything, but is that then appropriate to do a MRD test to see how deep the remission is?

 

Dr. Furman:

So the real important question should be whether or not that’s going to impact upon clinical management.

So MRD testing is easy, it’s noninvasive, it’s a peripheral blood test or a bone marrow biopsy, which I guess is only relatively noninvasive, and the information though is really not going to be of use.  So if you’re taking a patient who’s on ibrutinib and you’re going to continue the ibrutinib knowing the MRD status won’t change anything.  Likewise, if you have a patient who’s on venetoclax, who’s going to get a year of venetoclax on trial and then stop, knowing the MRD status won’t change anything as well.  So currently there’s no real reason for doing MRD assessments in patients except for just the ability to know.

Now, one day there’s some modeling that suggests that the time it takes you to reach MRD negativity is half the time you need to be on a substance, an agent, before you can actually claim to have a deep enough remission that you won’t relapse.  So we may one day say if you’ve been on ibrutinib for five years and became MRD negative, then 10 years of ibrutinib is enough and you can stop.  But that’s currently just theoretical and based on mathematical models.

 

Andrew Schorr:

Theresa wrote in, she said, my husband is being treated with acalabrutinib for five months.  He’s doing well, but should he have some sort of testing to know whether he will develop some sort of resistance in the future?

 

Dr. Furman:

So that’s a very important question, and the answer really is, you know, testing for it now isn’t going to be able to change anything.  Right now we would still continue the acalabrutinib until we see signs of clinical progression.  There’s some early data emerging from Ohio State where they’re doing PCR testing on all the peripheral blood of patients, on the peripheral blood of all patients to see whether or not they can detect any of these mutations that lead to resistance.  The problem is you’re still going to continue the treatment until you see the clinical relapse.

And, two, is you really‑‑you know, in essence when you look at the data that suggests that 92 percent of patients who get ibrutinib as a first‑line therapy will remain in remission at five years you’re talking about treating‑‑or testing a lot of people for very, very few people that will likely benefit.

 

Andrew Schorr:

Okay.  So if you have a question now, send it in, cll@patientpower.info, and we’ll do our best to pose it to Dr. Furman.  Okay.

So Beth with wrote in and wanted to know is there work going on on a CLL vaccine?

 

Dr. Furman:

So we’ve been playing with CLL vaccines for at least the past 25 years, and a lot of these vaccines were originally designed to be what we call antiidiotype, meaning they were directed against the antibody made by the cell itself.  Unfortunately, a lot of those vaccines have not proven effective, and we’ve gone through a lot of different iterations.  We’re still trying, and hopefully one day we will have better success.

Right now a lot of our current research is focused on not so much the target that the vaccine should be against but ways to make the vaccine more effective.  Things like using PD‑1 inhibitors, which can actually make the tumors more apparent to the immune system.  Or using things that can actually enhance the presentation of the actual vaccine to the immune system, and that includes everything from idelalisib and ibrutinib to other different molecules that may actually make it more readily apparent.

Now, we do also have some new targets like ROR1, which may prove to be very exciting and interesting, but this is still all very far away from anything that will be approvable.

 

Andrew Schorr:

Okay.  Now, here’s a question we got in from Cerisa, said, my understanding is that most drugs aim at destroying the CD20 protein like rituximab or obinutuzumab, etc.

Well, what about, CD9, CD15, CD23?  Are they not as bad as CD20 in CLL?

 

Dr. Furman:

So the thing that’s really important to keep in mind is only our monoclonal antibodies attack one protein in particular, and so we have obinutuzumab, rituximab, and ofatumumab all of which address or target CD20.  CD20 was the first protein targeted for two reasons.  One is it’s ubiquitously expressed on all B‑cell lymphomas, and so it’s a way to identify a target that we can actually generate one treatment for that will work in a large number of people.

The second is it’s a protein that doesn’t seem to actually get endocytosed or down modulated so that it remains positive in the cases most of the time.  One of the problems with some of the other proteins you mentioned is that they’re not expressed on the CLL cell.

So CD3, CD15, those are not present on CLL cells, but they’re also present on a lot of other cells as well.  The key about CD19 and 20 is that they’re only on B‑cells, and we really can actually do okay without our B‑cells.  And so that way the down side to knocking an out all our B‑cells is actually relatively minor.  And the CAR‑T cells, which are T‑cells taken out and reprogrammed, they’re reprogrammed to be directed against CD19 and 20, so in a way they work like the monoclonal antibodies.

 

Andrew Schorr:

Okay.  Lynn wrote in and asked about transplant in CLL, and I’ve met people who have had transplant, so where does transplant fit in now, and does CAR‑T cell experimental therapy maybe supersede that?

 

Dr. Furman:

One well, one of the things that’s important to keep in mind is that CAR‑T cells are still very novel, and the long‑term efficacy is not yet there, so we still need to do a lot of work to help that.

My belief is allogeneic transplants are very effective but they’re also very toxic and dangerous, and I do believe that they should be avoided if at all possible.  So I am very, very selective in who I refer for allogeneic transplant.

With our novel agents like ibrutinib, idelalisib, duvelisib, umbralisib, acalabrutinib, vecabrutinib, zenabrutinib, the list is just rapidly growing, I almost believe that the patient who really needs an allogeneic transplant will only be those patients who have developed or are at high risk of developing Richter’s transformations.  So I really do believe there’s a very limited role for allogeneic transplant at this point in time.

 

Andrew Schorr:

Okay.  And CAR‑T, you’re watching it.

 

Dr. Furman:

I am.

 

Andrew Schorr:

Okay.  Here’s a question that came in from Mike, and this is the bottom line for a lot of people when they’re diagnosed, and he says, what is the current state of treating CLL for those of us watch‑‑he says wait and see patients or watch and wait.  In other words, is it curable?

 

Dr. Furman:

So right now CLL is not curable.  The way that I would love everyone to start approaching CLL is very analogous to high blood pressure.  So we don’t cure high blood pressure, but if you take a pill a day it’s not going to have an impact on your longevity.  And I believe we’re there for about 75 to 80 percent of CLL patients, where they will be able to get a BTK inhibitor or a Bcl‑2 inhibitor or a combination and they will be able to not have to worry about their CLL for the rest of their lives.

There’s still the 20 percent who are going to develop either a Richter’s transformation or a progression on ibrutinib, and those are people we’ve got to figure out what to do differently for.  But all the others, even though it’s not curable, we can definitely I think keep it from having an impact on longevity.

People on watch and wait who are high risk of progressing and developing a Richter’s or progressing onto developing resistance to ibrutinib, we do have a couple of trials that are very interesting right now where we’re treating people at diagnosis with BTK inhibitors with the hope, because they’re so well tolerated and because they’re so effective, we might be able to have an impact and prevent those patients from developing resistance or developing a Richter’s transformation.

 

Andrew Schorr:

Wait a minute.  So are we looking at what has been the traditional watch and wait period differently now and some people will be treated much earlier?

 

Dr. Furman:

Well, we’re just starting to look at that right now in clinical trials.  So this is very early.  It’s for a very select group of people.

We know from the data‑‑so we have seven‑year data coming out at ASH this year where we’re going to have a group of people who were watched and waited and only when they had evidence of disease progression and needed treatment and got ibrutinib, 92 percent of them were still doing well and free from progression at seven years.  So for those 92 percent of patients we couldn’t do any better.  So it’s really just a very small group of patients who need something extra.

So, yes, we’ve proven I think in a large number of patients that BTK inhibitor therapy might be all that’s necessary, but in everyone else, in those 8 percent we do have studies going on to try to answer how to treat them differently.

 

Andrew Schorr:

Okay.  So we got a question early on about somebody who was asking about should he be taking a statin along with his oral therapy for CLL.  So people have other conditions.  So what about that?

 

Dr. Furman:

So if you have hyperlipidemia you should definitely be on a statin, otherwise, no, you don’t need a statin.  I think it’s important to keep in mind that there was a lot of data generated at one point about statins perhaps changing the CD20 expression on the surface of the CLL cells or making rituximab or other anti‑CD20 antibody therapy more efficacious.  I’m not aware of any data that suggests there’s an impact to statins on non‑anti‑CD20 therapy efficacy, and I think the impact on anti‑CD20 antibody efficacy is actually really quite small and unlikely to generate a significant difference.  So I really don’t believe there’s a need to do anything outside of just treating your lipids.

 

Andrew Schorr:

I promised our audience weeks ago that I’d ask you about this.  So should we have flu shots?  Should we have the shingles vaccine?

 

Dr. Furman:

So, absolutely.  Everyone should definitely get a flu shot each year.  And it’s important to get the flu shot each year because the immunity doesn’t persist.  So I actually recommend people get vaccinated either October or early November.  All right?  So any earlier than that I worry that you’re going to have your immunity peak before the height of the season, and later than that you may not actually have sufficient time to respond.

Regarding the shingles vaccine, so there’s a new shingles vaccine called Shingrix which is a recombinant vaccine, so it’s not a live vaccine, and that’s how it’s different than the previous shingles vaccine.  The previous shingles vaccine was an attenuated or live virus vaccine, and CLL patients really shouldn’t have taken it because it really theoretically could have caused shingles.

Now, the old shingles vaccine was also not very effective, so even though the risk was low with low efficacy there’s really no risk/benefit assessment that puts it in favor of doing.

But the new shingles vaccine actually has been tested in patients post autologous bone marrow transplants, so it’s very effective in patients who are very immunosuppressed, and because it’s not a live vaccine it is safe.  So I do recommend it for everyone.

 

Andrew Schorr:

Okay.  Dr. Furman, so you mentioned it earlier and we’ve heard about a lot of programs, the 17p deletion and I almost think of it as the dreaded 17p deletion, but is that necessarily true?  Pam wrote in, she said, I have the 17p deletion.  What are my options?  So first of all, are all 17ps alike, and then what are the options?

 

Dr. Furman:

So the thing that’s most important to keep in mind when we talk about prognostic markers is they’re really just surrogates for clinical behavior.  And so the answer always is going to be if you have historical data that’s always going to trump the prognostic marker.

So someone who is 17p deleted and their disease has remained stable for the last five years, their disease is stable, and the 17p deletion is not going to be what drives the prognosis.  I think that’s very important because when you look at a curve you’re going to see some people doing well and coming off the curve late and some people doing poorly coming off the curve early.  You know, where they are on the curve we have no idea how to predict.  All we know is that they’re on a particular curve.  So prognostic markers tell us about the population, never about the individual.

Now, with that being said, we do know 17p deletion a lot of it, the percentage of the deletion if you’re above 20 or below 20 does have an impact on how you do overall.  So 20 percent and below, they‑‑patients seem to have a better prognostic outcome than the patients who have 20 percent and above.

With that being said, I do have patients who have 17p deletion in 70 percent of their cells and they’re just hanging out doing quite nicely.  So clinical behavior does trump everything else.

 

Andrew Schorr:

Okay.  So, obviously, most CLL patients are older.  I’m 68 now, but I was diagnosed at 45, which is pretty young, but here’s Matthew who writes in he was diagnosed at age 31 and he wonders, he knows a lot of the statistics but he knows it’s mostly older people.  He’s trying to figure out, well, what’s his life going to be like.  So what do you say to younger patients with CLL today?

 

Dr. Furman:

So, remember, we’ve only had these novel agents since 2010, and so what I really do believe is that we really don’t know how good things are going to be yet.  I think things are going to be a lot better than we ever envisioned, so I am quite optimistic about the future.

We don’t know whether or not a 31‑year‑old could enjoy a normal long life expectancy but if they don’t have evidence of or suggestions that they’re going to have particularly aggressive disease and develop resistance to a BTK or a Richter’s transformation, they could theoretically have 40 years on a BTK inhibitor.  And so that’s certainly what my hope is for the future.

You know, all the survival curves that people talk about and all the survival curves that people show really don’t take into account any of the novel agents, and that’s always very important to keep in mind.  So we do some have data.  As I mentioned, the seven‑year data is coming out from‑‑will be out at ASH, and the seven‑year ibrutinib data really suggests almost a nearly flat curve for patients with CLL who get ibrutinib as a front‑line treatment.

 

Andrew Schorr:

So you mentioned over the years the Rai staging system, and Dr. Rai, the grand old man of CLL.

So how does that apply now?  You know, somebody’s diagnosed with CLL, they come across this Rai staging system, but is that meaningful for them today, or are there new ways of looking at it?

 

Dr. Furman:

So the Rai stage really still drives when we’re going to treat patients.  So patients are still treated based on meeting, you know, the classic indications for initiation of therapy.  So Rai stage 3 and 4, namely hemoglobin less than 11 or a platelet count less than 100,000, really are the two primary reasons why people initiate therapy.  We know that if you watch and wait someone until they meet classic criteria and they have disease that doesn’t harbor one of these high‑risk changes we know that they’re going to do extremely well.  So that’s good news.  Whether or not patients who have these other markers should be treated before they have aggressive disease is on open question.

Now, what I really do think that’s also important to keep in mind is, you know, the watch and wait ideology really came about when we had therapies that were not very effective and also were quite toxic.  Now that we have these novel therapies that are far less toxic and highly effective, maybe the bar should move towards initiation of therapy sooner, but that’s still on open research question and not one that we know the answer to yet.

 

Andrew Schorr:

Okay.  And Bob has had the same treatment I’ve had.  He had Gazyva or obinutuzumab with high‑dose methylprednisolone, and now that was, gee, about two years ago, and now his CLL has started to show up in his spleen and his lymph nodes.  He said, well, can he be treated with the same combination again, or might he move to something else?

 

Dr. Furman:

Well, that’s going to depend on a lot of factors.  Most importantly is whether or not there was, you know, he had received the full dose in which case the likelihood is that with just a two‑year remission I would expect that retreatment would generate a shorter remission this time, and the risks associated with high‑dose methyl prednisolone plus obinutuzumab probably don’t outweigh, or aren’t going to be‑‑the risks are going to outweigh the benefits that would be gained if we’re talking about a response that’s going to last less than two years.  So it would probably be better to move on to additional agents.  And, fortunately, we have so many others that I think it would be a way to avoid resistance and also develop‑‑avoid, actually, the toxicities associated with high‑ dose methylprednisolone.

 

Andrew Schorr:

Okay.  We’ll take just a few more questions, and thank you, Dr. Furman, for sticking with us.  And I relate to this one.  So I did have the obinutuzumab and rituximab years ago, and I developed sort of a history of sinus infections for a while and even some chest congestion and I’ve seen other people write in about it.

Do we have the sinus or the respiratory issues from the CD20 antibody or is it something else?

 

Dr. Furman:

So it’s important to recognize that CLL patients, 75 percent of CLL patients will develop hypogammaglobulinemia, and that hypogammaglobulinemia is probably most of the cause of the chronic sinusitis, chronic bronchitis, sort of that‑‑those issues with having the constant drainage.  So I do believe that CLL in and of itself is certainly the first factor that impacts upon that.

The anti‑CD20 by itself will also cause a lot of those problems as well, so the two together are just a double hit.  But we do know that CLL patients, totally regardless of their prior‑‑regardless of their prior treatments will run into those issues.

Now, with that being said, what people often forget is the most common cause of a chronic sinusitis in anyone, even a CLL patient who’s gotten obinutuzumab, is still going to be a deviated septum,  or it’s going to be a blocked sinus channel, so I always recommend and I always insist on all my patients being evaluated by an ear, nose and throat doctor first just to make sure there isn’t something anatomical that could be fixed.

 

Andrew Schorr:

I went to an ENT the other day, and also I’ve been doing‑‑and I know my Dr. Kipps here is urging me, I’m doing the nasal wash and all that stuff, just trying to have sinus hygiene, if you will, working on that.

Okay.  Couple more questions.  Aukie wanted to know, and we’ve talked about this in the CLL world forever, should he be taking a green tea extract?  Is there any validity for that?  What do we know?

 

Dr. Furman:

So my belief is no.  I think it’s important that we have a lot of alternative medicines, medicines that have been studied, and until they show evidence clinically I do believe that it’s important to actually stay clear of them, and there are a couple of reasons why.

So a lot of things work in the laboratory, but that doesn’t mean they’re going to translate into working clinically.  And a lot of the medications that are sold as alternative medications or homeopathic medicines are unregulated and can make claims that aren’t substantiated, but they also don’t have their products necessarily vetted.  So we’ve had a number of examples of people who have been taking a root or have been taking some leaf that’s turned out to be laced with amphetamines.  So a leaf that claims to enhance your energy output, absolutely, if it’s laced with amphetamine will certainly be able to accomplish that.

So it’s important to keep in mind that anything that’s made naturally or that occurs naturally doesn’t actually get regulated the same way as pharmaceuticals.  There was also a change in the laws in the 1990s where anything that was natural didn’t have to be tested and approved by the FDA, so the claims that they make‑‑like Tony the Tiger can say that Frosted Flakes are great without proving that in a randomized controlled clinical trial.  Because it’s a naturally occurring substance it can make claims that aren’t necessarily substantiated.  I do worry about that.  And there are some definite cases of patients coming to harm from taking medication‑‑from taking supplements that weren’t well regulated.

 

Andrew Schorr:

So, as you know, so many of us complain about fatigue with CLL.  What can we do about that?  Is there any medication or something you feel comfortable about as a supplement that could help with that?  Certainly, we’ve been telling people exercise is a good thing and can give you more energy, but what do you tell your patients when they talk about fatigue?

 

Dr. Furman:

So this is actually a very common question, and I really do believe it’s very important to remember that having CLL doesn’t protect you from the things that befuddle the rest of us.  So the most common cause of fatigue in a CLL patient is not going to be the CLL but it’s going to be the same thing that befuddles the rest of us.  So it’s poor sleep hygiene.  It’s not sleeping long enough.  It’s all those things that really should be addressed first and foremost.  So we see a lot of sleep apnea that’s undiagnosed.  We see a lot of people who are just not sleeping long enough.

If we’ve ruled out everything else and a patient seems to have progressive disease, yes, there are definitely patients with CLL whose fatigue is related to the CLL, but I’m a big believer that fatigue related to CLL should only be present in a patient who really has active signs of CLL.  So if someone is on watch and wait and their lymphocyte count is not changing and their lymph nodes are not enlarged, their fatigue is not going to be related to their CLL.

But if someone’s lymphocyte count’s climbing and their lymph nodes are growing then certainly their fatigue might in part be related to their CLL.

 

Andrew Schorr:

Okay.  This has been like being on a game show.  I keep throwing things at you.  I want to thank you for all your time.

Folks, we’re going to let Dr. Furman go, but we will be doing other Ask the Expert sessions and doing some live broadcasts in from ASH.  ASH, you alluded to, Dr. Furman, always has more coming out, more longer range studies, combination information.  So just to wrap up with, for those of us living with CLL, and, thank god, so many of us long term, me, 22 years, are you very hopeful that you have more options for us now no matter what our CLL situation is?

 

Dr. Furman:

I really do.  I think we have some amazing options now.  We have also the data that our current crop of novel agents really can be safe and effective long term, and that’s what I really think is so important to be cheerful about.

And in those patients who do progress we have a whole crop of other agents that will prove to be hopefully effective in those situations.  But I think it’s going to be the‑‑you know, the home run though is going to be the combination of BTK and Bcl‑2 inhibitor therapy or PI3 kinase and Bcl‑2 inhibitor therapy because in those situations I really do see patients getting very, very deep remissions that I hope will be extremely long lasting.

 

Andrew Schorr:

Think about it, folks.  I mean, I got FCR, a three‑drug combination, in 2000, 18 years ago, and it worked for a long time.  So the idea of combination therapy has worked well in cancer therapy hitting those cancer cells in multiple ways.  Dr. Furman, thank you so much for being with us today.

 

Dr. Furman:

My pleasure.

 

Andrew Schorr:

Okay.  From Weill Cornell.

And I just want to mention for our audience, remember we’ve got a lot coming up.  On Wednesday, November 28, we’re going to understand the ins and outs of watch and wait for those of you who are in that situation.  From the big ASH meeting in San Diego‑‑yay, I don’t have to get on a plane to go anywhere‑‑we’ll be also doing live broadcasting so be sure to be signed up for that.

And then on December 5th we’re going to talk about the financial issues because, as Dr. Furman talks about, combining these oral therapies, these are expensive, and so what support is there for you so you get the combination should you need it and it’s affordable.  So keep an eye on that.  Go to the Patient Empowerment Network’s website, powerfulpatients.org, and take a look at what we have on Patient Power as well.  Thank you so much, Dr. Furman.  Thanks to our audience and stay tuned for what comes out of the ASH meeting.  I’m Andrew Schorr.  Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

How Do We Increase Precision Medicine’s Reach in Lung Cancer?

Living Well With Lung Cancer

In this webinar in partnership with H. Lee Moffitt Cancer Center & Research Institute, Dr. Jhanelle Gray, a medical oncologist, Dr. Stephen Rosenberg, a radiation oncologist, and Dr. Theresa Boyle a molecular pathologist will discuss the latest understanding of lung cancer research; currently approved therapies and promising clinical trials.

Downloadable Guide


Transcript:

Andrew Schorr:   

And greetings from here, San Diego-Carlsbad, California. I’m Andrew Schorr from Patient Power. Welcome to this Patient Empowerment Network program. I am so excited. It is really a wonderful opportunity for anybody dealing with lung cancer. Whether you’re the patient or you’re a close friend or a family member, to get the latest information.

So, let’s meet that team. I wanna start with a medical oncologist and that is Dr. Jhanelle Gray. And she is director of thoracic clinical research in the Department of Thoracic Oncology at the Moffitt Cancer Center. Dr. Gray, thanks so much for being with us.

Dr. Gray:                

Thank you very much. It’s a pleasure to be here.

Andrew Schorr:   

Okay. We’re gonna understand the role of the medical oncologist. But it’s a bigger team than that. So, I wanna also have us meet Dr. Stephen Rosenberg who is a radiation oncologist and works in concert with medical oncology. He’s normally down in Tampa, but today – where are you in Wisconsin, Dr. Rosenberg?

Dr. Rosenberg:    

I’m currently in Madison, Wisconsin giving a talk later today and tomorrow. 

Andrew Schorr:   

Okay. Home of the University of Wisconsin. Thanks for joining us.

And then there’s another member of the medical team none of us usually get to meet. And that is the pathologist who’s looking at our biopsy. Whether it’s taken from the lung or now increasingly liquid biopsies, our blood, and we’re gonna talk about that. And that is a pathologist and that is Theresa Ann Boyle who joins us. Dr. Boyle, thank you for being with us.

Dr. Boyle:               

Thank you for inviting me. It’s nice to be dragged out from behind the scenes.

Andrew Schorr:   

All right. Well, you won’t be beside the scenes anymore.

And of course, all of this – we have this whole group, but it doesn’t mean anything unless there’s a patient that they can help and maybe a family with them. So, let’s meet a patient from Tampa who’s been living with lung cancer for a number of years, Ed Cutler. Ed, thank you so much for joining us on this program and we’re gonna share your story. Hi, Ed.

Edward Cutler:     

Hi. It’s a pleasure to be here and an honor to be honest with you.’

Andrew Schorr:   

Well, Ed, so, you’ve been living with lung cancer how many years now? 

Edward Cutler:     

Just over five years.

Andrew Schorr:   

Okay. But let’s face it, it wasn’t that long ago if somebody was told they had lung cancer they were not long for this world with more advanced lung cancer. So, modern medicine has made a big difference for you, hasn’t it?

Edward Cutler:     

It certainly has. When I received my diagnosis, I was given the quote average life expectancy statistics and they didn’t look very good.

Andrew Schorr:   

Right.

Edward Cutler:     

So, I went the whole way.

Andrew Schorr:   

And we should mention that for the last couple years you’ve been in a clinical trial and it’s an immunotherapy. And we’re gonna talk about immunotherapy along the way. We’re gonna talk about target therapies, immunotherapies. The doctors are gonna help us understand this whole idea of precision medicine. Which means, “How do you get what’s right for you?”

And you’ve had some changes along the way, right Ed? I mean there you are in Tampa continuing your work as a tax consultant, I know. And been married more than 50 years to Donna, which is great. Children and grandchildren. But you’ve had kind of a journey that’s had changes along the way, right?

Edward Cutler:     

It has been a journey. Yeah. Yeah. Initially I started out with standard of care chemotherapy. And that basically took over 16 months. Basically, the first two or three months I was on the full medication of three drugs. And then they dropped off one and then I was on maintenance. But at the end of the 16th month they discovered that there was a new tumor. And I was told I was now chemo-resistant and that was the end of chemotherapy for me.

So, my etiologist and I sat down, and we started searching. And at that point, I don’t think there were any other approved medications. Everything else I think was still in trials at the time. Now I know that there are maybe two, three, a half a dozen medications that are out of trials and FDA-approved. But at that time, I was limited to clinical trials. And Dr. Tan, who is my oncologist, gave me the options looking at two or three different trials. And my goal was to live as long as possible with good quality of life. And that’s what I was looking for in each of the trial descriptions.

And we ended up selecting one and I took all of the various testing to qualify for that trial and I was ultimately accepted. It was a two-drug combination of infusion. And unfortunately, I only lasted seven – roughly seven months in that trial because of side effects that almost killed me. 

Andrew Schorr:   

But now there’s another trial?

Edward Cutler:     

And fortunately, it took another few months, but we located another trial that was being performed only at Moffitt. I said, “Well, that’s convenient.” So, I said, “Yeah.” Everything looked good on that. Sure, there were potential side effects, but I was willing to take my chances with it. And here I am nearly three years into that trial and I’ve been stable most of that three-year period. There was a little bit of tumor size reduction initially and basically stable the rest of the time. It’ll be three years come the end of January.

Andrew Schorr:   

That’s such great news.

So, Dr. Gray, you have lots of trials at a major center like Moffitt, maybe you could just tell us in this world of lung cancer, patients who participate in trials have not only paved the way for everybody, but it’s given them great hope, hasn’t it?

Dr. Gray:                

Absolutely. So, we have a lot of trials at Moffitt. We try to organize ourselves within a way of doing a personalized medicine approach. And basically, that means that any patient that comes to Moffitt we wanna give them the best treatment possible. And many times, that is a clinical trial. With clinical trials a lot of times you have access to more novel agents and things that you can’t necessarily get through your regular route through FDA approval. And also, a lot of that work is spurred by research developed here at Moffitt and partnering with the basic science researchers as well as us at a lot of the clinical – on the clinical side and making sure that we move these drugs forward and into the clinic for patients.

And Edward, I just wanna say I’m very happy about your story. And thank you for taking the time today to be with us and to share your journey with us. And give us your perspectives to this too.

Andrew Schorr:   

Yes. It’s very inspiring to all of us. And Ed, we know you’re a golfer. And so, you’ve been… 

Edward Cutler:     

Well, I was.

Andrew Schorr:   

Well, please God you can do that and travel with Donna. And the main thing is you are with us.

Dr. Gray:                

Yes.

Andrew Schorr:   

And I know that means so much to you and your family.

We’re gonna talk about the team approach as we go forward. So, Dr. Rosenberg, radiation oncology comes into play here because often when somebody’s diagnosed radiation can help shrink the tumors, right? And also alleviate some of the pain and other issues that people may have, right?

Dr. Rosenberg:    

Yeah. No. I think you hit on a lot of big major points there. And it really is a team approach. Particularly at Moffitt when we approach lung cancer trying to think about how we can do best for the patients, whether it’s a clinical trial or not. Radiation plays a big role for patients who have a locally advanced disease. Some of the standard of care is combining chemotherapy with radiation for patients with some advanced disease. But for patients who have had cancer spread to other parts of the body as well, radiation’s really good to help alleviate pain and even approve breathing and the other things that are happening.

And with newer agents we often find that radiation may even be potentiating the immune effects of some of the new immunotherapy drugs that are out there. And so, we’re really excited about some of the trials and studies we’re doing with Dr. Gray and her team. And the team as a whole at Moffitt combining irradiation with some of their new – with targeted drugs and immunotherapy drugs right now.

Andrew Schorr:   

Wait. Let me see if I get that. And Dr. Gray, feel free to comment too. Are you saying that radiation can sort of boost the effect of some of these medicines?

Dr. Rosenberg:    

Yeah. There is a lot of anecdotal evidence out there. And some basic science that’s right now emerging about how the immune system and radiation really are so interconnected. And how that helps us actually attack cancer by actually basically releasing the immune system to recognize the cancer in the body. And so, by combining that with immunotherapy drugs we’ve really found our ability to potentiate some of the effects of these immunotherapies.

Most of this is basic science. There are some anecdotal case reports out there with some of the newer drugs that have just come out in the last year or two FDA-approved have been after chemoradiation and we think they really work together well. And some of the newer trials at Moffitt are gonna be trying to combine these things up front. And I know Dr. Gray has been helping to lead that effort with Dr. Perez and others within our kinda joint departments here.

Dr. Gray:                

Yes. Absolutely. And so that work that Dr. Rosenberg was just talking about was actually developed at Moffitt. So, there’s a trial out there that’s now published in the New England Journal of Medicine. It led to the FDA approval of a drug called Durvalumab, which is actually named because the company, AstraZeneca, wanted to add durable responses and add value to patients. So, Durvalumab is where the name came from, interestingly enough.

And the study, what we wrote, was to look at those patients getting chemotherapy plus radiation therapy completing what’s considered standard of care therapy for those patients with that particular type of non-small cell lung cancer. And following this with an immunotherapy agent, the durvalumab (Imfinzi), for one year. And it significantly improved the outcomes for patients. Patients are living much longer when we utilize this method.

And now this has become the standard here in the United States. It’s working its way through the approval mechanisms over in Europe and through other companies. And I think this has really revolutionized how we approach and treat patients. And we are looking at – now we know it’s safe to give them sequentially. And so, can we safely and effectively – meaning can we actually improve outcomes for patients by moving these therapies upfront?

And so, it would be giving a lot of therapies together. So, it would be chemotherapy plus immunotherapy plus radiation therapy to patients. But at the end of the day, the goal here is to improve our outcomes in a – and still maintain quality of life for patients. So, it’s always challenging pushing the bar and reaching these goals for our patients.

[Crosstalk]

Andrew Schorr:   

Right. Right.

So, Ed, just a little bit more about your story and then we’re gonna bring Dr. Boyle into this too as we talk about personalized medicine. So, when you were originally diagnosed, you were, I think, consulting with a doctor about a concern about an aortic aneurism. It had nothing to do with cancer.

Edward Cutler:     

Yeah.

Andrew Schorr:   

You went to one doctor and then maybe a GI specialist. That’s where they found a mass. And then you went to Moffitt and saw a lung cancer specialist. Did I get that right?

Edward Cutler:     

That’s right. Yeah. The triple-A test, the Abdominal Aortic Aneurism test, was negative. But down at the bottom of the report in the footnote was that they saw a mass in my liver and follow-up was recommended. So, we went from there. I went to my primary care and he referred me to a GI doc and they pretty much agreed that there was some kind of cancer, but they didn’t know what exactly. They recommended that I get a PET scan, which Medicare would not permit. They said you have to have a diagnosis before you can get a PET scan.

So, the alternative was to have the biopsy. I said, “Okay. But let me get a second opinion first.” And that’s when I came out to Moffitt and they confirmed everything. I had my biopsy here at Moffitt. And there was a tumor in my liver, but the biopsy traced it back to my lung. Therefore, I have lung cancer.

Andrew Schorr:   

Right. And I wanna explain that. Okay. So, let’s start with Dr. Boyle on that. So, Dr. Boyle, you look at the biology of tissue samples or sometimes blood.

Dr. Boyle:               

Correct.

Andrew Schorr:   

And so, somebody says, “Oh, I have liver cancer.” But that just came up where he said well, he didn’t really have liver cancer, he had cancer that originated in the lung and the biology of it was it needed lung cancer treatment, right? And that’s part of what you figure out, right?

Dr. Boyle:               

Right. Right. Right. And actually, within the pathologist group there’s different fields of pathology. There’s the anatomic pathology where they’re looking at the diagnosis, “Is it lung cancer origin or is it kidney cancer origin?” I’m in the field of molecular pathology. So, I’m looking at the genetic changes inside the tumor, or in the blood too, and I’m trying to understand what those changes might mean in terms of what would be the best therapy for the patient. I’m also in the lung cancer research field. So, trying to better understand all of these immune checkpoints and how can we look at them. Why do some patients respond, and others don’t respond?

So, pathology is a large field. So, I’m working very closely with the thoracic department. In fact, I belong to them. 50% of my job is with the lung cancer department and 50% with the pathology department. And we found that that was helpful because the field is expanding so dramatically. Even within every year there’s great advances. And for anyone to keep up with everything is too difficult these days. And so, we really do all work as a team here at Moffitt. And so, as Jhanelle and I talk back and forth – a lot of emails with.

Dr. Gray:                

Right. Yes.

Dr. Boyle:               

So, I even consulted them on some of these questions you have. So, it’s great.

[Crosstalk]

Andrew Schorr:   

All right. Well, we’re gonna delve into this personalized medicine world. And the doctors will help us understand. We’ll understand how it applies to patients like Ed or others who may be watching. So, let’s put up the personalized medicine slide. Kat is our director and she’ll put it up.

I have a little dog barking here. I’m sorry.

Dr. Gray:                

No, you’re fine.

Andrew Schorr:   

Very cute.

Dr. Boyle:               

I like dogs.

Andrew Schorr:   

Kat, if you could put up this slide? There we go. Okay. So, help us understand – let’s start with you, Dr. Boyle.

Dr. Boyle:               

Yeah.

Andrew Schorr:   

This whole wheel around the right, what is this alphabet soup there? What is it?

Dr. Boyle:               

Right. Right. Right. So, this is showing the variety of different genes that can have genetic changes in the tumor. And it’s focused on the genetic changes that have potential clinical action or proven clinical action. EGFR is probably a more familiar one because that one came out first with better responds to EGFR inhibitor therapy than chemotherapy and others have come along. Like with ALK, ALK inhibitor therapy works well. With MEK, XM14 has become important, MET amplification.

Andrew Schorr:   

Okay. These are genes that have gone awry that are driving someone’s cancer, right?

Dr. Boyle:               

Correct. Right. Right. Right. And this wheel is trying to pick up on the driver mutations. There’s even more genes not on this wheel here that are passengers. Other mutations that might have some specs, but they might not necessarily be causing the tumor or driving the tumor but might be worth considering in terms of the therapy. In immunotherapy, tumor mutations burden has been something we look at. And they’re looking at many, many gene changes to see if there are more mutations than usual. And when that occurs, there might be a better likelihood of response to immunotherapy. So, we’re learning more and more everyday about all of these genes and more.

Andrew Schorr:   

Okay. We’re gonna define this. And Dr. Gray, you can help us. These kinda big bubbles to the right.

Dr. Boyle:               

Yes.

Andrew Schorr:   

So, first of all, a myth: All lung cancer tumors are the same. This right here says, “No,” right?

Dr. Gray:                

No. Absolutely. Yes. The fact is that each patient’s tumor has a unique biology. And the wheel on the left I think really helps to define this. That at the end of the day when we get a patient we’re concerned about, we get a biopsy, get a piece of tissue, send it over to pathology to Dr. Boyle’s team. She’s not only looking under the microscope to help us with, “What’s the diagnosis? What’s the origin of the tumor?” But we also wanna look at, “What is driving your tumor?”

And so, how I’ve explained it to patients is in two ways. You have a computer that has all these different parts, but at the end of the day what drives the computer is really that hard drive. And if you open up the hard drive there’s this little piece of hardware that’s actually making everything run. And that’s what we’re doing with the tumors is going into the cell, looking at the DNA level and seeing what is turning on your specific tumor.

Another way of thinking about it is as a hub for an airline, for example. So, a lot of us know Delta has a very big hub in Atlanta. They have a lot of flights that go through there. But if you were to shutdown Atlanta you would significantly impact the feasibility of Delta being able to function.

And that’s what we’re doing by looking at these driver mutations. We wanna find what’s turning on your tumor and then match that patient to the correct medicine. So, if you have the EGFR mutation, I wanna give you an EGFR inhibitor. If you have an ALK rearrangement, I wanna give you an ALK inhibitor. If you have a MEK mutation, I wanna give you a drug that targets MEK. What I don’t wanna do is if you have an EGFR mutation give you an ALK inhibitor. I’m doing you a disservice.

And so, it is very important – I think you brought up a very good point at the beginning of this that the team approach for lung cancer is imperative so that we can all work together to get the right patient the right treatment at the right time. 

Andrew Schorr:   

We’re gonna look at a graphic for that in just a second. I wanna just go over a couple of other things you mentioned. So, somebody might have a lung biopsy. Get some tissue. That goes to Dr. Boyle and her colleagues.

Dr. Gray:                

Yes.

Andrew Schorr:   

Wherever in the world you get treatment. And they’re taking a look at it to see where in this wheel – what comes up for them?

Dr. Gray:                

Correct.

Andrew Schorr:   

And then also there’s a – in that purple bubble there it says, “Tumor testing can happen at any point.” And so, we talked about driver genes.

Dr. Gray:                

Yes.

Andrew Schorr:   

And then Dr. Boyle mentioned passenger genes.

Dr. Gray:                

Yes.

Andrew Schorr:   

Well, they can change over time, right? 

Dr. Gray:                

Correct.

Andrew Schorr:   

There’s an argument for having testing again at some later time, right?

Dr. Gray:                

Absolutely. And so, for example, if you have an EGFR mutation and I give you an EGFR inhibitor, you then have a chance that your tumor can mutate against that specific drug that I’m giving you. And you can acquire a different mutation. And so, how do I know what’s going on? I need to get more tissue or – I don’t know when we’re planning on talking about it, but this is a good segue into liquid biopsies.

So, a liquid biopsy is getting a blood sample from patients and looking – specifically looking again at this wheel, looking at those mutations to see if we can identify them.

Andrew Schorr:   

Okay. 

Dr. Gray:                

And so, it is very, very important to keep monitoring patients, getting their blood, getting their tissue over time so we can make educated decisions. Again, just to relate this to something I think we’re all very familiar with is infections. If you keep giving the infection the same antibiotic, what happens? It develops resistance. And these drugs are no different and cancer’s no different. It’s just we have to stay ahead of the game and try to keep trying to outsmart the tumor.

Andrew Schorr:   

Right. Right.

[Crosstalk]

Dr. Gray:                

So, absolutely monitoring.

Andrew Schorr:   

Many researchers and specialists talk about cancer being really a wilily enemy.

Dr. Gray:                

Yeah. Enemy. Yes.

Andrew Schorr:   

And so, you can knock it back. But there’s sometimes the survival of the fittest of some cells that have some other property, like another gene?

[Crosstalk

Dr. Gray:                

Yes.

Andrew Schorr:   

So, Dr. Boyle, just help us to understand this idea of liquid biopsy. Because I know over the last few years sometimes there’s been a concern – I don’t know who does it. Whether a surgeon does it. Who does it? To get a lone biopsy and as much tissue as they can. But you’re saying, “Well, I need more to make other decisions.” Where does liquid biopsy come in now, basically a blood test, to help inform targeted, well-informed lung cancer care?

Dr. Boyle:               

Right. Right. Yes. Pathologists always want more tissue, but now we have an alternative. And sometimes an alternative gets the results faster back to the oncologist and the patient. And that’s the blood testing. And it has less risk than taking a sample from the lung. Now, the interpretation of the results from the liquid or the blood specimen is a little different than the interpretation from a tissue specimen. And when you get a positive result from the small amounts of cell-free DNA circulating in the blood, you can really count on it. And the oncologist can treat the patient with a targeted therapy based on that.

There are times when the results are all negative and you don’t know if the results are negative because there just wasn’t enough cell-free DNA in the blood or because the tumor is truly negative for all the mutations being checked. And so that’s where it really is important to follow-up with tissue testing. So, it’s been really a great advance in the field to be able to test with a specimen that’s much more easily available and can be tested right away.

Andrew Schorr:   

I’ve had the opportunity to tour foundation medicine back in Boston area and also be in some labs at other hospitals. And I’m amazed that these super sophisticated analyzers now to try to see what’s going on, whether the blood or the tissue

Okay. So, we’re gonna come back to where does that go out? I wonder if Kat, our director, could put up the personalized medicine slide? One more time, Kat. No, not that one. We’re gonna come back to that. That one.

So, there’s that whole area, Dr. Gray, on the left where it says, “Other.” And I know that Dr. Boyle and her colleagues around the world are trying to say, “Well, are there driver genes that we just haven’t identified yet?” And you keep having these analyzers looking at more and more, a bigger – 100, 200, and 300 whatever.

Dr. Gray:                

Yes.

Andrew Schorr:   

But some people, and I think this was Ed’s case. There wasn’t a driver gene that was identified.

Dr. Gray:                

Right.

Andrew Schorr:   

Well, what do you do there? 

Dr. Gray:                

So, one of the things that we’re testing for in addition to these driver mutations is also looking if patients may be a better candidate for immunotherapy and looking at a marker called PD-L1. It’s programmed death-ligand 1 which can be found on the tumor tissue cells. So, most patients will undergo simultaneous testing for both the immunotherapy marker as well as one of these driver mutation markers. So, if we’re unable to find a driver mutation, but we’re able to find that the tumor’s positive for PD-L1, that then triggers to us, as a medical oncologist, that, “Hey. We need to kind of shift and let’s focus on getting the patient immunotherapy.”

And particular now with the approvals and the trials that we’ve participated in here at Moffitt, as well as at other centers, that really if you have lung cancer, you don’t have a driver mutation. Outside of having a specific rational why you shouldn’t get immunotherapy, really you should be starting on immunotherapy.

I just wanna make – within that setting I just wanna make something clear. There are also some patients where you can find a driver mutation and you can find that they’re positive for the marker for the immunotherapy. And how do you choose between the two? For right now, most of the data points toward that you should focus on treating the driver mutation. That that does take precedence over the PD-L1, the marker for immunotherapy, okay?

And I know there’s a lot of commercials out there and a lot of excitement about immunotherapies for very good reason, but I would reserve the immunotherapy in those subsets of patients who have both markers to maybe a later line of therapy. But that also gives you a backup plan, right? It’s to your point you’re always trying to project and sequence things for the patients as much as we can. So, it is helpful to do both markers upfront and then act accordingly.

Andrew Schorr:   

Okay. I wanna make a point. I think that we’re done with this slide now. I wanna make a point that some people – it’s the minority, but it’s still a significant group – don’t have non-small cell lung cancer. 

Dr. Gray:                

Correct. 

Andrew Schorr:   

They have small cell lung cancer. And this has been tougher. But my understanding, and Dr. Gray, maybe you can inform us, that in some of the latest meetings you’ve been learning that immunotherapy along with chemotherapy can make a difference for people with small cell lung cancer, is that correct? 

Dr. Gray:                

Yes. Yes. That is absolutely correct. So, at our recent world congress on lung cancer meeting – now, this is our global international meeting for lung cancer where all the lung cancer experts get together now on a yearly basis. A lot of that has to do with that so much is changing that we now need to meet yearly. We used to meet biyearly.

One of the key presentations there that was in the presidential symposium seat or that’s the big session there was looking at combining chemotherapy with immunotherapy versus giving chemotherapy alone. And when they looked at this in patients with newly diagnosed, what we consider extensive stage or most people refer – may refer to it as stage four small cell lung cancer, that those patients derived a bigger benefit if we did the combination therapy. So, we’re talking about going from two IV infusions now to three IV infusions. So, you do add an hour, but there’s significant benefits that we all feel is also clinically beneficial for these patients.

If you happen to have small cell lung cancer and you are on chemotherapy there is also data that following your chemotherapy that utilizing immunotherapy in the subsequent line can also be helpful. So, these data are showing us consistently that immunotherapy is certainly effective in small cell lung cancer. And thank you for raising that point and that distinction. 

Andrew Schorr:   

Okay. So, Dr. Rosenberg, I’m gonna bounce this off of you as a cancer specialist. Not particularly about radiation but let me see if I get it right because we’re talking about immunotherapy.

When I developed cancer – and I’ve actually developed two blood cancers. So, I’m living with it. But whatever the cancer is, our bodies let us down, right? Our immune system has let us down and we’re starting to create aberrant cells, right? And they can develop masses like Ed had and they can spread. There’s a certain biology that the other doctors were talking about that they try to target. But with immunotherapy, that’s trying to leverage our immune system to do what it didn’t do right the first time, is that right? Is that the way you see immunotherapy? 

Dr. Rosenberg:    

Yes. Very much so. And one of the things that can define cancer is its ability to evade the immune system. In terms of our normal body, the way our immune system is set up is set up to go around our body and take care of any precancerous cells and try to destroy them. And unfortunately, what cancer does it has molecular mechanisms that try and basically get around these things. And so, the immunotherapy drugs that are out there help release the break in terms of the immune system to go back and attack these cancer cells.

And in terms of the interaction with radiation, because I am a radiation oncologist and I tend to bring it back there, is that what radiation can help do in that setting is actually destroy some of the cancer cells and kind of release what we call antigens into the blood stream or the nearby tissues to hopefully help the immune system better recognize the cancer. And when you take the break off the immune system and then allow the immune system to hopefully better recognize the cancer cells, these things all work together moving forward.

And so, I think there’s – only as we move forward, we see more interactions with radiation and the immune system and even these targeted therapies. I know that we went over – Dr. Boyle and Dr. Gray talked about how – these new targeted therapies that are out there. But even from a radiation point of view, we’re now really pursuing radiogenomics where we’re actually using some of these genetic signatures actually to determine how cancers respond to radiation treatment. And we’re actually sculpting our radiation to actually target certain areas of tumors to higher doses or lower doses based on some of these molecular mechanisms.

And it’s a really exciting time. And Moffitt particularly is really pioneering both of these areas to kinda push the boundaries in science right now.

Andrew Schorr:   

Well, good for you.

And I think, Ed, in listening, with this new age of cancer care it really argues wherever possible for people to get a second opinion at a major center like Moffitt where this brain power and leading edge of research can be brought to bear, wouldn’t you agree?

Edward Cutler:     

Oh, absolutely. No question about it.

I do have a question for Dr. Boyle. And that’s going back to the wheel of the mutations. Go back to 2013 when I was diagnosed, were all of those mutations tested when I had my biopsy or has the state of the art evolved such that now they do test for all of them? Or are there still some that they don’t test for until a certain event occurs?

Dr. Boyle:               

Right. So, there is still some disparity about where you go for your care and how many genes are tested. Certainly, Foundation One has a very large panel of genes. And I believe that was available in 2013. At Moffitt in this past year we validated a 170 gene panel that tested both the DNA and the RNA at the same time so that we can detect fusions like ROS1 and ALK at the same time as we’re detecting EGFR, KRAS, BRAF. All things on the wheel.

And so, I mean that only became available this year. In the past it was more piecemeal. And so, there were certain things that could be tested early on and possibly more things tested later. More and more we’re doing more comprehensive testing early on at diagnosis so that we know more at the beginning.

Andrew Schorr:   

I think there’s a point to underscore here is the field is evolving. The other day, Dr. Gray, we did a program that included someone you know from Harvard, Dr. Siegrist. And her advice, and I think you’d echo it, is wherever our audience gets care you wanna get a broad panel testing. And as we’re hearing from Dr. Boyle, the panel’s increasing, but the downside – and I know patients like this, for instance, with one of those more rare driver genes, ROS1, where they were tested sequentially and given, as you said, the wrong therapy for a while until they finally got around to doing the right tests and knew what was going on and did what’s right for them.

Dr. Gray:                

Yeah.

Andrew Schorr:   

So, I think for our audience, wherever you get care, and certainly it happens at Moffitt, you want a broad panel and as Ed was getting at is that panel is expanding.

Dr. Gray:                

Yes.

Andrew Schorr:   

What’s going on for you, and I think what you all say, and personalized medicine is, the right treatment for the right patient at the right time.

Dr. Gray:                

At the right time. Yeah.

Andrew Schorr:   

Okay?

Dr. Gray:                

Exactly.

Andrew Schorr:   

Okay. Let’s go to the role. We have another slide that describes the role. Really the team medicine approach, if you will. And let’s take a look at that.

So, okay. So, Ed was referred to Moffitt. Came there for a second opinion. And so, let’s see how it goes. So, Ed was the first place you went was to an oncologist. Was that first stop for you?

Edward Cutler:     

That’s correct.

Andrew Schorr:   

Oh, okay.

Edward Cutler:     

I went to a GI oncologist.

Andrew Schorr:   

A GI oncologist? But then it was discovered that it was really coming from your chest. And there was testing done. So, Dr. Rosenberg, let’s let you lead it. So, here I see radiation oncologist, medical oncologist, way down at the bottom we have molecular pathologist, like we have Dr. Boyle. How does all this work together?

Dr. Rosenberg:    

I think you’re gonna hear this theme over and over again, but it’s really a team with all of us. Especially say we meet to go over patients in a weekly tumor board which includes both our medical oncologists, radiation oncologists, surgeons, our pathology colleagues, our radiologists. It’s really all of us together. And so, as we gather information from a new patient, we’re trying to really determine what their stage is. Usually first of all based on imaging and then trying to establish a diagnosis through the tissues that we’ve gotten.

And once we kinda have that information we can meet as a team and kinda come up with a comprehensive treatment plan. And that includes gathering not only the tissue information, but the molecular information that Dr. Boyle really helps us put together there. And then after we have all that information gathered then we can kinda go down these different paths depending on what stage the patient has, what their molecular drivers are, and what sort of clinical trials and opportunities we have available for them that fits them in a very personalized way which really goes back to that personalized medicine that you were talking about there.

Andrew Schorr:   

Dr. Gray, any comments from you about this wheel? 

Dr. Gray:                

No, I completely agree with what Dr. Rosenberg summarized. I think we’re at – we’re a big referral center at Moffitt Cancer Center. And many times patients may come in with a biopsy. And I wanted to just touch base with what was mentioned before about getting enough tissue. When you do do biopsies to work up for the lung cancer that is very important. And I think this wheel here and this summary here helps to highlight that. That we really want to get down to the point where we’re really collaborating with the molecular pathologist looking at your biopsy within the lab. And perhaps getting that circulating tumor DNA analysis in a blood also to make this decision.

And I fully concur that this is a team approach. We really need the pathologist to let us know what’s going on. We really need to sit down as a team and make sure that we all come up with the right decision for the patient. And that’s certainly one of the benefits of going to a place like – you mentioned Harvard and coming to the Moffitt Cancer Center certainly also.

Andrew Schorr:   

Right. So, Dr. Boyle, so there are people listening who maybe have had a biopsy somewhere else. Maybe at the community level. And here, you’ve got this big lab and you have other groups that you work with with huge analyzers and pathologists and all that that you work with. Somebody says, “Well, if I come to Moffitt” – oh, any other major cancer center, sometimes the request is made to have another biopsy or other tests. Why is that important today? Because do you have sometimes where maybe the initial analysis wasn’t as correct as it could be?

Dr. Boyle:               

Right. It’s kinda like the bane of our existence. People like to say the tissue is an issue.

Andrew Schorr:   

Nice. 

Dr. Boyle:               

And it goes along with the “if you don’t have an adequate specimen you can only get so much information out of it.” The blood testing has really helped alleviate some of that pain, but when a procedure’s going to get a small bit of tissue from the lung, it can be less than 100 cells. And we’re trying to do the best we can to learn about 100 tumor cells. So, that’s why the biopsy is so important. And I was thinking maybe we can go around the wheel. We are missing the surgeon in here, but I love this appearance and how you can go around and around and around.

Andrew Schorr:   

Right. 

Dr. Boyle:               

But the patient usually first comes in and sees their oncologist and then a biopsy can be taken, and it goes to the anatomic pathologist and they determine is it adenocarcinoma or squamous cell cancer, small cell or some other primary cancer.

And then the specimen get to genetic testing. They go to the lab and that’s where we come in. We’re looking, “What’s the tumor cellularity? Is it enough for us to even test? Can we test with the targeted small panel if it’s not enough for big next generation sequencing panel?” And we do the sequencing on our big fancy machines, but we get the results. And it really requires pretty intensive interpretation to understands the results and make sure that we’re reporting out accurate results.

Andrew Schorr:   

Yeah. I wanted you to speak to that. There’s an art to – there’s an art to medicine.

Dr. Boyle:               

Well, yes. 

Dr. Gray:                

Yes.

Andrew Schorr:   

Of course. But there’s an art to pathology. And so, you wanna give accurate recommendations of what are we dealing with to the medical team, the rest of the medical team, and that has an art to it, right? And you’re a subspecialist in that area.

Dr. Boyle:               

Okay. Right. And we don’t want to overwhelm oncologists with too much information either. So, we’re very receptive to feedback about what’s most important for actually taking care of your patients that you’re seeing. And the resistance mutations have become very important. We used to only check for one part of the ALK gene and we got feedback from the oncologist that that wasn’t good enough. They need to look at all of the ALK gene for resistance mutations. So, back and forth.

And then we also have the help of the personalized medicine group here at Moffitt. And that’s wonderful. They have [inaudible] [00:47:19]. So, they know about drug side effects. They know how to work with insurance companies. They know how to answer questions about what’s the functional effects of genetic changes. So, when we send out a report, it goes straight to the oncologist, but it also goes to the personalized medicine group for a more in-depth look. And maybe some help identifying clinical trials that the patient might be newly eligible for based on the genetic findings.

And the radiation oncologists have become more involved too. As Stephen was talking about how the genetics can play a role in the care in terms of the radiation. There’s more and more clinical trials that are getting involved in together to better understand what’s the best therapy.

Andrew Schorr:   

So, Dr. Rosenberg, what I’m getting from this is a patient might see Dr. Gray or see you or maybe a surgeon with earlier stage lung cancer as well, but that there’s this whole group – Dr. Boyle, but she rattled off a few other groups as well that are all behind the scenes. And you guys are talking about me, the patient, right?

Dr. Boyle:               

Oh, yeah.

Dr. Rosenberg:    

Yeah. Absolutely. I think that we are really in communication with each other on a pretty regular basis as a team. And I think that’s what really leads to this personalized care for the best outcome for the patient is really being very communicative about – between Dr. Gray and between Dr. Boyle, between the surgeons that we work with and just everybody really working together to try and make the best decision we can for each patient.

And gathering all the right information upfront. I think that’s really the key is making sure we have all the right information we need, whether it’s molecular or imaging, before we go down a certain path, so we don’t go down the wrong path for any particular patient. And yeah, I think as we kind of put that information together we can help really personalize each person’s care that way. And from a radiation point of view we’re using both the imaging information that we’re getting and the molecular information to help make radiation decisions.

And at Moffitt, we’re really trying to push those boundaries from imaging as well. And we talk about personalized care from these molecular changes, but Moffitt, this room will be opening up our MRI-guided radiation treatment unit which is the first in the country. There’s only a handful of places that are doing MRI-based radiation treatment. And that’s really another form of personalized care by seeing somebody’s anatomy up close and in a very particular way and designing the radiation based on individual anatomy. And so, with that better imaging we’re able to do that. So, there’s a lot of ways to personalize care for patients moving forward.

Andrew Schorr:   

So, Dr. Gray, I wanna talk about the spread of cancer. So, Ed talked about how he had this on his liver. But you figured out – you all figured out it came from his lung?

Dr. Gray:                

His lung. Yes.

Andrew Schorr:   

Lung cancer can spread. Cancer can spread generally. But here we have people with metastatic cancer who are living longer with some of these approaches. 

Dr. Gray:                

Yes.

Andrew Schorr:   

Radiation, immunotherapy.

Dr. Gray:                

Therapy.

Andrew Schorr:   

Targeted therapy. 

Dr. Gray:                

Different therapies.

Andrew Schorr:   

So, when you tell somebody, “Mr. Jones, yes, you’re right. Imaging, we see your cancer spread.” That’s not the end of the story.

Dr. Gray:                

Absolutely not. No. So, what we also look at are these genetic findings, the pathology findings, the markers for the immunotherapy. But at the end of the day what your goal is is to extend life and to add quality of life to patients. And so, as we look at this information, we want to make sure that we’re making the right decisions. And this is the goal ultimately of personalized medicine.

Yes, your cancer may have spread, but we can give you treatments that are gonna knock down the cancer, get it to shrink down, and to a point that sometimes may become undetectable on the scans. We do think that there’s cells still circulating there, but we could still continue to follow you and keep track of the cancer and make sure that you’re – we’re helping you to manage this properly.

Andrew Schorr:   

Okay. So, I wanna remind our audience, send in your questions. This is an ask the expert question. We have an expert patient who’s lived it. And I know Ed, you spend time talking to other patients and family members. We have Dr. Boyle and we got her out of her lab there.

Dr. Boyle:               

Yeah.

Andrew Schorr:   

You might not see her in the exam room, but she plays a key role. We have Dr. Rosenberg who’s even travelling and joining us. And Dr. Gray. So, if you have a question send it to lung@patientpower.info.

And I wanna tackle a question. Here’s one we got from Gretta, “What percentage of blood biopsies are accurate?” She said, “I had one done and it showed I no longer had the BRAF mutation, but subsequent tissue biopsy showed I did still have it. So, how reliable are the liquid biopsies?” And I think you, Dr. Boyle, mentioned that a little bit.

Dr. Boyle:                                 

Right.

Andrew Schorr:   

So, this is a new area of pathology. In this area, how much can you rely on it?

Dr. Boyle:               

Right. So, the positive results we are finding when you’re testing with a reputable company they are – can be very reliable. Just as reliable as the tissue testing for the positive results. And there are some advantages even. Because in the body you might have a tumor on the lung that’s a little bit different from the tumor that spread to the liver, whereas the blood is a big mixing bowl. And if you have some DNA sloughing off the two different tumors, that DNA is mixing in the blood. So, you’re getting a more comprehensive look at the mutations in the blood.

One big, big disadvantage that’s represented in this question is when you get a negative result. When you get a negative result like she got for her BRAF in the blood, it’s really a non-informative result as opposed to a negative result that you can hang your hat on. Because you don’t really know how much cell-free DNA is actually sloughing off the tumor and circulating in the blood. And so, if it’s not in the blood, you might get a negative result when really, it’s still BRAF positive in the tumor as she found when she had this tissue tested again.

Dr. Gray:                

Positive.

Andrew Schorr:   

But this is evolving, right? I mean we couldn’t even talk about liquid biopsies not too long ago. So, the sophistication and the sort of getting down almost Nano – the Nano-level, you’re working on it, right?

Dr. Boyle:               

And that’s what Jhanelle and I have talked about this so much with algorithms for how to really understand the results and use the results.

Dr. Gray:                

Yes.

Dr. Boyle:               

And this is something that – at Moffitt we know well about the negative results being more like non-informative results with the blood. And we find them very helpful when we interpret them appropriately. 

Andrew Schorr:   

Okay. Well, there we go to the art and the sophistication of the tools that continue to develop. So, a lot of computing power folks that go into this. And then the wisdom of folks like Dr. Boyle.

All right. Here’s a question we got from Greg. I think this is for you, Dr. Gray. “What is happening in research for those of us who do not have target therapy gene mutations and also have a low tumor burden. Is chemotherapy the only option?” 

Dr. Gray:                

No. So, if you look at the studies that have occurred so far, looked across the patients that have a low tumor burden or have a negative PD-L1, or have no actionable or driver mutations, we still know that chemotherapy plus immunotherapy’s the way to go. We’re also doing a lot of research in that setting is that once those or if those stop working for you, what are gonna be the next steps? And that I think is certainly an area of need. One of the things that we’re looking at is combination immunotherapy strategies. That perhaps giving you one immunotherapy therapeutic agent was not enough and that you perhaps need two.

I think that chemotherapy is still very important. And doing combination strategies down the line with some of these novel agents. When we look at some of the – a lot of the trials, even the ones where you give chemotherapy with immunotherapy, if you look at the data, most of the benefit upfront, for now at least, appears from the actual chemotherapy. So, chemotherapy is very good at reducing disease bulk. But the immunotherapy can then come in and activate – help to activate your immune system. And the ultimate goal of immunotherapy is to create immune memory, okay?

Almost along the lines of a vaccine. You get your flu vaccine once a year because it mutates. You get your hepatitis vaccine. You’re not getting it every year. You only get it for a sequence. And the purpose there is that your immune system should be able to sustain on your own. And we wanna do that for patients upfront. That would be the ideal. But we also recognize that we just – this is very new, and we don’t know enough.

So, I think expanding more in combination immunotherapy strategies, looking at novel agents, looking at where chemotherapy’s target also and probably repurposing those drugs a little bit so that we can actually hit the target even better than regular systemic chemotherapy and reducing toxicities. There is a plethora of research going on within all avenues.

So, I think the key thing there is that if you have something and it’s not working for you, come to a center of excellence like Moffitt Cancer Center and sit down and talk to us and we can let you know. And exactly to your point. We talk to physicians all across the globe. Work very closely with Dr. Siegrist at Harvard. We share patients. Share data constantly. Even if we may not have something for you here at Moffitt, there may be somewhere else in the United States that we can send you also.

So, I would not – I don’t think – the key thing there is that giving up should not be the first option by any means.

Andrew Schorr:   

Amen. I just wanna drop back for a second and make sure everybody understands this whole world Dr. Rosenberg talked about a little bit. So, the immune system let us down. And Dr. Boyle a while ago used this term checkpoint.

Dr. Gray:                

Yes.

Andrew Schorr:   

So, Dr. Graham let you be the professor here. See if I get a good grade. The cancer cell has this kind of protective world around it where medicines traditionally maybe don’t kill it. 

Dr. Gray:                

Yes. Correct. Correct. 

Andrew Schorr:   

Right? Okay. So, what the immunotherapies are doing, maybe more than one, is to knock down that barrier.

Dr. Gray:                

Yes.

Andrew Schorr:   

So, that whether it’s with radiation like Dr. Rosenberg talked about with these immunotherapies where your immune system can do its job in killing the cancer cells, the abnormal cells.

Dr. Gray:                

Yes.

Andrew Schorr:   

And you also eluded to something else where the immunotherapy can continue to do this surveillance wherever the cancer may be. Whether it’s spread to Ed’s liver, whether it’s gone to somebody’s bone.

Dr. Gray:                

Yes.

Andrew Schorr:   

Wherever it is it says, “Oh, now I see you.”

Dr. Gray:                

Yes. 

Andrew Schorr:   

“And guess what? Bad news. I’m gonna kill you.” Right? 

Dr. Gray:                

Kill you. Correct. 100% right. So, one of the ways to think about this is that the immunotherapies, if you see the commercials out there, for example, for Opdivo or Keytruda, they actually do not kill the cancer cells. So, this is very different than chemotherapy. Traditional chemotherapy we’re very used to goes in, actually kills the cancer cells. Exactly. The immunotherapies are unmasking the tumor to the immune system allowing the immune system to now recognize the cancer cell as foreign and then attacking the cancer cells. And exactly, your immune system should then sustain on its own. And that is the ultimate goal of immunotherapy.

Andrew Schorr:   

And Ed, that’s what you’ve been living with, right? You said earlier you’re stable. So, you’re taking immunotherapy and it’s kinda knocking it back, right?

Edward Cutler:     

Yes, it is. To what Dr. Gray said with respect to, I guess, first line of treatment with the combination of chemo and immunotherapy, what is the standard now with the combination? Is it Alimta, Avastin and then Keytruda or Opdivo?

Dr. Gray:                

Yeah. So, right now as of 2018 what is approved by the FDA – I’m just going back a little bit. Remember there’s two main types of lung cancer. There’s small cell lung cancer, there’s non-small cell. There’s two main types within non-small cell of a non-squamous type of lung cancer and then a squamous cell type lung cancer. And to Ed’s point, he’s completely right, your chemotherapy that we choose for you depends on your type of lung cancer. And I think that’s what you’re alluding to in the question.

Edward Cutler:     

Yeah. Yeah. 

Dr. Gray:                

So, there are data that has shown for non-squamous, non-small cell lung cancer if you combine Carboplatin plus Pemetrexed plus Pembrolizumab together, that is the FDA-approved regimen for first-line – for that type of non-small cell lung cancer.

Now, if you have non-small cell lung cancer and the subtype is squamous cell, the drugs that are approved right now are Carboplatin, Paclitaxel, plus Pembrolizumab. Or you can substitute that Paclitaxel for something called Nab-Paclitaxel or Abraxane. Paclitaxel can cause some infusion reactions in patients. And so, the Nab-Paclitaxel is formulated to minimize that infusion reaction. So, there’s some flexibility there, but they’re still in the same class there.

So, and then if you have the small cell lung cancer actually the regimen that is approved there is a platinum – so cisplatin (Platinol) or carboplatin (Paraplatin) plus Etoposide plus etesolismab. So, it’s really even within that spectrum these are all ways of personalizing medicine for patients. And really having that level of information from the pathology and the biopsy side so that we can make the best decision for the patients. 

Andrew Schorr:   

Okay.

Dr. Gray:                

And then when that data comes in is having that expertise about which one is gonna be the right for which patient.

Andrew Schorr:   

Right. But there’s one other aspect I wanna put on. So, for patients, whether you go to Moffitt or another major center, rather than some of those names she mentioned, there may be a clinical trial where it has a number.

Dr. Gray:                

Yes.

Andrew Schorr:   

And it says, “We’re gonna give you X, Y, Z, 1, 2, 3, 4. That’s what we recommend,” which hasn’t been approved, but they believe may offer a better option for you.

Dr. Gray:                

Yes.

Andrew Schorr:   

Did I get it right?

Dr. Gray:                

Yes. Correct. And so, we call them license plates, right? License plate numbers. And so, when the drug first comes out of drug development, it kind of gets this license plate number and Nivolumab, Pembrolizumab, all of them came out with these license plate numbers as we call them. And then you just – as they move forward, and they show promise that they then develop a more formalized name – nomenclature for the naming. But to your point, it is very important to also look at clinical trials within that setting. That’s how we make these strides. That’s how we make these improvements.

We participated in a very first trial with Nivolumab here at the cancer center and I still have a patient that is alive six years out. His daughter was five when I met him. She’s 11 now. They sent him to hospice on the outside and I said, “You know what? We’re gonna try this medication.” And he has not received the immunotherapy in four years. And this is a perfect example where his immune system was able to work, get the tumor down, and now it’s sustained on its own off therapy. And if he didn’t come to Moffitt, he would’ve just been sent to hospice.

Andrew Schorr:   

Okay.

Dr. Gray:                

So, this is where exploring – making sure that you explore all of your options is very, very important. What I always recommend, you know what? Can you get treated locally? 100%. But at least go in for that consultation. Make sure that there’s not something newer, more novel, something that we think may be a little bit better. Clinical trials is always a way to explore things. At the end of the day the standard of care FDA-approved therapies are always there, and we can always give them to you whenever. You may have this option for this trial. And I think my patient got one of the last slots on the trial nationally. And I think… 

Andrew Schorr:   

…wow. What a story. I just wanna recap a couple things for our audience, okay? So, you got it now about personalized medicine and getting what’s right for you, whether it’s one of these targeted therapies in this growing list of genes that Dr. Boyle has talked about. And drug companies and government working to development things that match up with that. Immunotherapy, maybe more than one. Some that have a commercial name and some that have a license plate like Dr. Gray just described.

And then this whole idea of radiation oncology where Dr. Rosenberg and his colleagues are finding out how does all this work together? How can radiation actually trigger something in a cancer cell that then also helps it say to the cancer drug, “Hi, I’m here.” Boom. They get hit by a cruise missile, right? So, that’s what they’re working on.

All right. We’ve got a bunch of questions. Remember, lung@patientpower.info. This one came in from Leo. And Leo says, “Any new research or treatment regarding patients with the TP53 mutation?” So, first of all, Dr. Boyle, what is TP53? 

Dr. Boyle:               

Oh, goodness. I don’t off the top of my head know how that spells out, but it is a tumor suppressor protein. And it’s a gene which we find frequently mutated in all cancer types. And it often causes a worse prognosis. And there are many researchers trying to see if there are better drugs to target therapies. And lung cancer, the clinical trials are pretty early. The highest you get is phase one and two. So, there has not been a lot of success yet. In leukemia I think there’s more phase two trials.

We have an excellent researcher here, Elsa Flores, who is looking at animal models in vivo studies to try to understand more. Now, one thing sort of interesting about TP53 is that if you have lung cancer with TP53 and a KRAS mutation, that mutation is gonna be more likely to respond to immunotherapy.

Dr. Gray:                

KRAS mutation. 

Dr. Boyle:               

There’s a really nice paper out by John Heymack about this if there’s also an STK11 mutation. So, then it’s a lower likelihood of response to immunotherapy.

Dr. Boyle:               

So, with more and more research we’re lending some of the nuances of these and we’re hopeful that there’s going to be more that can be done with the TP53 mutations in the future.

Andrew Schorr:   

Okay. So, Dr. Gray. So, you were nodding your head while she explained that? 

Dr. Gray:                

Yeah. Yeah.

Andrew Schorr:   

So, in other words, you’re looking at not just one gene being the bad guy, but this constellation in a given patient.

Dr. Gray:                

Right.

Andrew Schorr:   

And does that tell you something that you could do in a more refined way for them?

Dr. Gray:                

Right. I think this is we’re coming into a center where we have this level of expertise and we’re sharing data across the different centers. But exactly what Dr. Boyle noted is that when we look at these genomic reports, right, you’re getting a lot of information coming out back at the medical oncologist. And knowing how to fully understand and interpret that data so you can make the best decisions for the patient is very helpful.

So, if we see a KRAS mutation, the P53, without an STK11 mutation, certainly that will move immunotherapy up on for the armamentarium for the patient. Now, this is a little bit in experimental mode, but we’ve seen similar data here at Moffitt. And it’s really starting to pick up traction across different cancer centers and lung cancer experts.

Around the specific question of the P53 mutation, we do have a compound that we’re looking at here in collaboration with AstraZeneca. It came from a trial that I had written and am working on that came from work derived here from Moffitt Cancer Center. It’s called AZD1775. But it basically what it is is it’s looking at inhibiting the cell cycle. I’m gonna take us back to biology a little bit. And cells, how they replicate, basically they have to go through mitosis, right? You have to replicate your DNA and then split off and divide.

And so, what the P53 does is it’s almost – as Dr. Boyle mentioned, it’s a tumor suppressor. What does that mean? It actually puts a stopgap, an intentional stopgap when cells go to replicate. And it makes the cell stop and check and say, “Do I have any mutations? Should I move forward or not?” What cancer cells do is they’ve lost – they mutate the P53. So, they don’t get that stop in place. They just keep replicating. Even though technically these are abnormal cells, they’re damaged cells and they shouldn’t replicate themselves.

So, what that drug does is it intentionally incorporates – if you have that P53 mutation your cells are not stopping when they’re replicating abnormally. This AZD1775 helps to add that stop so the cells can check themselves and say, “Hey, you know what? We’re really not replicating ourselves properly. We should actually go towards cell death and not cell survival and replication.” So, there are definitely trials that are looking at the P53, to Dr. Boyle’s point, including one that was derived here. And as Ed mentioned, something that you can only find here at Moffitt. And we hope to have that data out maybe later this year or early next year.

Andrew Schorr:   

Okay. Stay tuned.

Here’s a question we got from Jim. “How does immunotherapy work in EGFR mutations after targeted therapies no longer work?” Do you wanna comment?

Dr. Gray:                

Yeah. Yeah. So, that’s a great question. So, one of the key things as I mentioned before is if you find a mutation such as the EGFR mutation you go down the realm of a targeted therapy. So, say to treat patients with a targeted therapy’s very, very important.

I wanna take this opportunity to say that you should not combine an EGFR inhibitor with an anti-PD1 with an immunotherapy. It significantly raises patient’s toxicity. So, if a physician ever – if that ever comes up, at least for right now, the answer, you should decline that, and no one should be offering that to you. Exactly.

So, I agree that the best way to incorporate them right now is through a sequential approach. So, you start with the EGFR inhibitor. And there’s four of them actually FDA-approved right now. So, you may get sequenced from one EGFR inhibitor to the next. What people are looking at right now is should we go straight to immunotherapy, should we go straight to chemotherapy, or should we go straight to a combination strategy of chemotherapy and immunotherapy?

I think based on the data for right now, most of us as long as we think that it’s safe will go to a combination of chemotherapy plus the immunotherapy based on the data. This is gonna be looked at more in detail to finally answer this question. It also depends on the wishes of the patients too. So, if you think that you cannot – if a patient cannot tolerate, for example, immunotherapy combination with chemotherapy, we may start with one or the other and then move on. But definitely I agree that the sequencing is gonna be the best way to do that.

Andrew Schorr:   

Okay. Let’s talk about the toxicity for a minute. So, Ed, you had – earlier you had some treatment that was pretty tough to take, right?

Edward Cutler:     

Yes. Yes, it was. The only major side effect that impacted me was colitis. But it was major. It was really, really major.

Andrew Schorr:   

And you had to change? You changed?

Edward Cutler:     

And when I read the protocol, yes, that was one of the potential side effects.

Dr. Gray:                

Right.

Edward Cutler:     

But that’s all it was was a potential side effect. I took my chance with it. I’d never had colitis before and then it hit me. And I’m still kind of dealing with that to some extent. Nowhere near what I dealt with three years ago.

Andrew Schorr:   

Okay. And your treatment was changed?

Edward Cutler:     

And my treatment was changed. Yes.

Andrew Schorr:   

Okay.

Edward Cutler:     

And that was a combination – a two drug combination trial.

Andrew Schorr:   

Yeah.

Edward Cutler:     

A phase one trial.

Andrew Schorr:   

Here’s a question we got in from Wendy. So, it’s a little technical, but she says, “I’m currently keeping my stage four non-small cell adenocarcinoma at bay with monthly maintenance infusions of Pemetrexed.” Did I get that?

Dr. Gray:                

Yes. Absolutely.

Andrew Schorr:   

“I was diagnosed in August of 2015. Nothing visible on PET scans, but the chemo’s been prescribed to keep the cancer reappearing.” And her concern is the long-term damage, she wonders, of getting chemo infusions over a long time. She says, “What could be the downside of chemo over a long term?” Dr. Gray?

Dr. Gray:                

Yeah. So, one of the things that we – well, congratulations. I’m glad that you’re doing so well. That’s really inspiring to hear. And I think that speaks to the fact that there are patients and cancers out there that respond to chemotherapy and I think that we should still keep that in mind.

The long-term side effects that we generally worry about with chemotherapy are how they affect your blood counts. And by blood counts, I’m talking about your bone marrow. So, your red blood cell counts. So, your hemoglobin and your hematocrit. Your white blood cell counts. Your leukocytes. Your neutrophils. Things that help you fight bacterial infections, viruses. And then your platelet counts. These really help with your clotting. So, if you cut yourself.

Pemetrexed, in particular one of the things that we’ve noted when you keep receiving this treatment in particular over time is that the anemia seems – can sometimes be a rate limiting step. So, I’d definitely keep an eye on your hemoglobin and hematocrit.

But I’ve had patients on these maintenance therapy agents for many years. A lot of times what I will do to lessen the burden for the patients. Normally the drug is infused as an IV infusion over ten minutes every three weeks. I will go to once every four weeks so that you’re only coming in once a month for a treatment to add more to quality of life. And then I’ll start increasing the frequency of the scans to less frequent. So, maybe quarterly you’ll get a scan instead of every six weeks. So, hopefully all these scans can help lessen the burden of the infusion and also help to improve quality of life at the end of the day. But I would certainly be careful of watching the blood counts within the study.

Oh, I think you’re on – are you on mute?

Andrew Schorr:   

Yeah. I’ve got it. Sorry.

Dr. Gray:                

Yeah? Sorry. 

Andrew Schorr:   

Dr. Rosenberg, related to toxicity you referred earlier about MRI-guided radiation. What are you doing in the radiation oncology field to get at the cancer, but not effect either healthy tissue – and also lower the side effects that can go with radiation. People that fatigue and other things that go along with it. And all of you have been talking about higher quality of life where you might be living with lung cancer.

Dr. Rosenberg:    

Yes. Yeah. It’s a great question. And I think how we’ve approached this in radiation oncology is actually by shortening our treatment courses. And as our technology has improved it will also give us very small volumes of irradiation with high doses to destroy cancer cells, but also sparing normal tissues. And as patients are living longer with lung cancer, we kinda have to say sometimes they’re responding well to chemotherapy or immunotherapy or targeted therapy, but one area is starting to grow, we use this targeted therapy called stereotactic body radiotherapy, SBRT. So, [inaudible] go after these important small areas that might be not responding appropriately or may even be resistant.

But these are targeted areas that we’re irradiating that are very small in volume. That’s really helped us limit toxicity, but to normal tissues going forward. And with the new MRI-guided treatment program, which is where my focus is gonna be, is that by having the MRI help us guide our treatment in real time, we can make our volumes even smaller. And by shrinking our volumes and targeting tumors more appropriately we can hopefully spare normal tissues and actually decrease side effects long-term for patients.

And so, again working with our medical oncology colleagues is that if there’s an area of resistance that pops up, an area that we can very precisely target, we’re still sparing a lot of the normal tissues in your body.

Andrew Schorr:   

Okay. Precision radiation oncology?

Dr. Gray:                

Yeah. Yes.

Andrew Schorr:   

Okay. 

Dr. Gray:                

And we do that also. And if I may add that if there’s somebody who’s on a treatment benefiting and they just have one area that’s kinda this rogue tumor that breaks through and becomes resistant, that definitely looping in the radiation oncologist, working with Dr. Rosenberg and his team, and targeting that specific area can be very effective for patients.

Andrew Schorr:   

Okay.

Dr. Gray:                

Before you switch therapy.

Andrew Schorr:   

Here’s another aspect of immunotherapy. So, we talked about these PD1, PD-L1 drugs, checkpoint inhibitors. So, another area that’s particularly happening in the leukemia’s that I know well is what’s known as CAR t-cell therapy, chimeric antigen receptor t-cell therapy. Where if I get it right, correct me if I’m wrong, you can sort of engineer t-cells to become sort of a targeted therapy.

Dr. Gray:                

Yes.

Andrew Schorr:   

All right. So, what about this in lung cancer, Dr. Gray?

Dr. Gray:                

Yeah. So, it’s a great question. So, one of the areas – this has really taken off in the hematologic malignancies are these CAR-T therapies. The hematologic malignancies are very well-defined by specific markers on the cells that are uniformly found across different types. So, lymphomas, leukemias. In the solid tumor realm, it’s been a little bit more of a challenge with finding where to specifically target. And also, to target the cells without adding significant toxicity to the patients.

So, we do have what’s called an ICE-T therapy here. It’s the immune and cellular therapy. It has medical oncologists on that team, both hematologists and hematologists. And they’re working together to help bring what we’ve learned from the hematology world over to the solid tumor realm. So, it’s new. I don’t think it’s yet ready for FDA-approval, but absolutely a very exciting, exciting field. Again, the purpose of these is to create these long-lasting responses with a personalized medicine approach.

Andrew Schorr:   

Yeah. I wanna thank Gordon for that question. I think we hear about – you mentioned TV commercials, or we see an article in the paper.

Dr. Gray:                

Yeah. Great question.

Andrew Schorr:   

And we say, “Oh, how does that apply to me?” Or, “Should we get on a plane and go somewhere because they’re trying this out?” It’s really tough. So, Dr. Boyle, you see this changing field.

Dr. Boyle:               

Okay.

Andrew Schorr:   

What would you say knowing what you know in going on and identifying new genes, if you had a family member – and I hope you haven’t, but if you had a family member diagnosed with one of these conditions, what advice would you give them? Because you’re on the inside. Or maybe you have friends or neighbors that call you up, “Oh, my God. We got this diagnosis. What should we do?” What’s sort of an operating system for patients and families today? What would you say?

Dr. Boyle:               

Right. Well, one thing I want to ask always, what Jhanelle was talking about earlier with the clinical trials, if you are getting the optimal standard of care plus whatever new innovative potential therapy might be available with those trials. And there actually is a better outcome with the participation in the clinical trials. They’re very carefully designed.

So, I would want a family member or a patient, it is the same, to get as much information as possible. And like Jhanelle said, it’s fine to get your care locally, but to get a second opinion at the most advanced center available to you for a second opinion. Get more information. See what’s available. Consider clinical trials. Sometimes just following the basics. Like if you have an EGFR mutation to get an EGFR inhibitor therapy and not be wanting say immunotherapy just because it’s the newest thing. That’s what I’d be thinking about. And getting the rapid care can be important too.

One thing I wanted to add onto what Jhanelle said earlier about the T-CAR conversation is that we also have a trial here with the tumor infiltrating lymphocyte. It’s not by definition a T-CAR trial, but it’s in lung cancer. And they’re basically taking lymphocytes out of tissue and growing them up in cell culture and reinfusing them into lung cancer patients in the hopes that the reinfused cells will attack the tumor. And I just think this is amazing progress that this being tried in lung cancer too.

Andrew Schorr:   

Here’s a point I wanted to make. So, I hope what all our viewers get – and I think we have some pretty savvy questions that have come in. The field is changing. And so, Dr. Gray, I’m sure when you went through your training there wasn’t always a lot to talk about with patients, right? 

Dr. Gray:                

Oh. No. That’s very true.

Andrew Schorr:   

And now we have people like Ed who are living longer, living pretty well. There are side effects we’ve talked about. Ed was talking about trying to limit that. So, the quality of life goes along with living well and living longer. But there’s a lot of progress being made, and you and your family have to be plugged into that. And yet, Dr. Boyle just referred to that. Don’t get excited about something just that you see on TV because it may not be right for your specific situation. And Dr. Gray was warning about that too. If you have EGFR, that’s not the time for immunotherapy, right?

Dr. Gray:                

Correct.

Andrew Schorr:   

Even though you saw the ad of people in town square. New hope for lung cancer. 

Dr. Boyle:               

On the highway. Yeah.

Dr. Gray:                

Yes.

Andrew Schorr:   

Yeah. So, you really have to – you really have to think about that. So, testing, broader panel, second opinion, team approach? 

Dr. Gray:                

Yes.

Andrew Schorr:   

We’ve got a wonderful team here.

Here’s a question that we got in. We just have time for a few more questions. But Helen asked this question, “Is there any research or anecdotal information on how much the drug Alimta adds to the efficacy of another immunotherapy Keytruda. Does it continue to be effective indefinitely or does it only work for a while?” Dr. Gray?

Dr. Gray:                

Yeah. So, there’s a recent study called the Keynote-189 study that combined Pemetrexed, Carboplatin, plus Pembrolizumab. So, Pembrolizumab is the immunotherapy. The Pemetrexed is the chemotherapeutic agent. And they treated those patients with the Pembrolizumab up to about two years.

The study was published, and it was found to be positive in the sense that it improved patient’s overall survival. So, how long were you gonna live? And also, what we consider your progression for your survival. How long did it take your cancer to actually progress to the point that we would need to switch your therapy? So, it was longer in that group than just giving the chemotherapy group.

You ask a very good question. These are the questions that we also, within the lung cancer field, are asking. How long do we really need to give these therapies for? Especially when you’re giving them in combination with immunotherapy when the goals of immunotherapy are to create long-term memory.

We have studies looking at giving immunotherapy for one year. We have studies continuing the immunotherapy indefinitely. And we have studies looking at giving the immunotherapy for two years. I think outside of the stage three – in the stage three setting, the clear data is that you give it for one year. Outside of that, I still think that it’s still a tossup. My suspicion is that you should at least probably go beyond one year if you can and see if you can’t get to the two-year mark. That’s where most of the data is at a minimum.

I actually have a patient now coming up on her two-year mark in February of this year on Pembrolizumab and I’ve started having those discussions with her and it’s an open discussion that, “This is what the data shows. What do you feel comfortable with?” And so, I think there needs to be a shared decision-making process within this realm also. And what the patient feels comfortable with and what the data helps to support. So, I think keep having those conversations, especially if you’re getting it combined with the immunotherapy. And hopefully there will be more to come definitively.

Just for a historical perspective, if you look back many decades ago when chemotherapy first came out, we used to give chemotherapy for a year. Then they did the trials where they actually looked at it at a year versus six months. The outcomes were the same with giving it over six months. And then they went from about six months versus about three months of therapy. And now went back a little bit, but added the maintenance in. And so, there’s definitely these trials will come, it’s just going to take time. The world of immunotherapy is very novel within the realm of lung cancer. And so, we have lots of growth to do.

But fantastic question. That’s probably one of the things that we sit and debate at our meetings very frequently.

Andrew Schorr:   

So, as we come near the end of our program, I wanted to get some final comments from our panelists. I’m gonna end with Ed because Ed, I want you to talk to other patients and family members.

But what I get from this is the field is pretty rapidly changing. Whether it’s in radiation and how that applies to other therapies. Whether it’s combination therapies, sequential therapies, duration of therapies we were just talking about with Dr. Boyle. It’s about identifying new genes or combinations of genes and trying to figure that out. So, what do you wanna say to a patient audience?

I’m gonna start with you, Dr. Rosenberg. So again, we have people all around the world and they or a family member has been given what’s a pretty terrifying diagnosis.

 Dr. Rosenberg:    

And it’s a scary time as they’re facing this. And actually, what I’m talking about here in Madison is actually putting together your medical and emotional teams as you’re basically facing this new diagnosis. And I think that’s the big thing is putting together a team and being someplace where you have the support and you feel comfortable. And also seeking out multiple experts to try to come up with the best plan you can moving forward.

And I think as Dr. Boyle, Dr. Gray, as the panels all alluded to, seeking that second opinion just to at least know what all your options are and are available to you is really important. Building your treatment team which includes so many different experts both that you’re gonna meet in person and behind the scenes. And I think that’s the real key aspect to this.

Andrew Schorr:   

Well, thank you for what you do. And this cool area you were talking about having radiation trigger a response in the cell that can make it more responsive to new medicines is really great. Good luck with all of that. Thank you.

Dr. Boyle, so you are a CSI detective. You are. You have like a magnifying glass.

Dr. Boyle:               

I love my job.

Andrew Schorr:   

Yeah. You have much more powerful tools than that. But you’re a sleuth. So, are you confident that this field is – will continue to expand to really unlock these secrets so you can say to these other team members, “Hey, I think this is what we’re dealing with and here’s a key pressure point to go beat that cancer.”

Dr. Boyle:               

Yes. Yes. I’m very optimistic. When we validated this 170 gene panel we did not even know if we would be reimbursed, but we did it anyway because we have so much optimism that it will have value and show value. And I really feel like understanding the cancer better. And it’s a key to better therapy. And my thinking is that patients should hold onto their hope throughout their whole experience and stand their ground. 

Andrew Schorr:   

Yes.

Dr. Boyle:               

Know what they want and don’t want and ask questions to their oncologist if they have questions. Because there’s a whole new world here and we’re all trying to figure it out together as a team. But we really appreciate the input from the patients as well. I think that’s helpful to helping all patients and future patients as well.

Andrew Schorr:   

Well, I wanna thank you for what you do behind the scenes as far as we patients and family members see you. But with your colleagues around the world continue to make these discoveries so that the therapies can be targeted or more broad. But whatever they are, know what we’re dealing with, so we get what’s right for you. Dr. Boyle, thank you for being with us too.

Dr. Gray. So, you have these partners here and we have patients and family members who you’re partners to. And as I alluded to earlier, in your own career you’ve seen a lot of change.

Dr. Gray:                

Yes.

Andrew Schorr:   

Is this a message of hope? And are you comfortable that more of us – even now we’re talking about small cell lung cancer where there’s progress being made that can extend life.

Dr. Gray:                

I’m very hopeful. I think that we have completely revolutionized how we treat patients – treat lung cancer and treat the patients battling lung cancer. We’re with you there right along helping you with that fight. And to your point, when I first started doing this I literally spoke to patients about chemotherapy. That’s what I had to offer. And it was just trying to make that selection process about which chemotherapy I thought was going to be right for you. And helping you with sequencing. “Okay, we’re gonna start with this and then we’re gonna plan for this and we’re gonna plan for that.”

And the game has completely changed, I think, with the genomic profiling. It is extremely important. We really have to go to these broad-based panels up front. And for right now, I just wanna emphasize tissue is the gold standard, but I really think that circulating tumor DNA is something that we can – certainly we’ve made a lot of significant progress and then can identify these mutations.

As you identify these mutations, checking them longitudinally over time to see how they evolve is gonna be very important. And that will help us continue to personalize treatment at what point do you pivot from a targeted therapy to a clinical trial to an immunotherapy to a chemotherapy. And all of these things come from sitting down, looking at the scans, looking at the patient, looking at these molecular reports, getting everybody on the same page and then making – again I think having a shared decision model. Setting, “What are your goals? What are your hopes?” And then making sure that we match that as best as we can.

Andrew Schorr:   

Wow. Get tested, folks.

Dr. Gray:                

Yes.

Andrew Schorr:   

Have your family member get tested and then raise the question with your team, “Do we needed to be tested again?” 

Dr. Gray:                

Yes. Yeah. 

Andrew Schorr:   

All right.

Dr. Gray:                

Absolutely.

Andrew Schorr:   

And then I think Dr. Gray, I just wanna underscore a point she made about your goals. 

Dr. Gray:                

Yes.

Andrew Schorr:   

So, Ed thinks about that. And Ed, I’m gonna give the final comments to you about speaking up for yourself.

Dr. Gray:                

Yes. 

Andrew Schorr:   

How do you get the care that’s right for you and how do you wanna live your life? I mean you and Donna wanna do some more traveling, right, Ed? I hope you can.

Edward Cutler:     

We’ve been very fortunate. No question about it. When I first got my diagnosis, I was devastated. I thought my world was gonna end in a year. But I started talking to my doctors, started talking to other patients in similar situations and I found that, yeah, there was hope. I put together a bucket list. And I found that my bucket list wasn’t gonna be limited to a year. So, I expanded my bucket list. And now it goes on at least ten years out now and I’m very hopeful of that.

As I said, I’ve spoken with a lot of patients here within Moffitt, around the state, around the country, and some internationally through support groups. And we help each other. We cry on each other’s shoulder and then we tell each other our problems. And somebody has an experience that they went through and it might be helpful to another patient. Now, I think it’s very important to open up your heart and open up your ears and your mind and listen to other people. Don’t just look at what you read on the internet. Who knows what the truth is what you read on the internet. A lot of it is – I don’t know. It’s not necessarily factual.

But I think if you talk to you doctors, to your team, and your team doesn’t include just your doctors. It’s your nurses, it’s the nurse’s aide, it’s the social worker, it’s the nutritionist.

Dr. Gray:                

No. 

Edward Cutler:     

All of these people can be very helpful for just about everybody who has an advanced diagnosis.

Andrew Schorr:   

Well said, Ed. We have this medical team here that represents some of those others that Dr. Boyle mentioned, the personalized medicine people, the pharmacist, you mentioned social workers. Before we have to go, I wanted to give you the chance if you want to say thank you to these folks or what they represent on behalf of patients. What would you wanna say?

Edward Cutler:     

I am just so thankful to every person that I’ve dealt with here at Moffitt. They have made the process if not the simplest thing in the world to deal with, pretty darn simple anyhow. My doctors have explained things to me that I didn’t even know how to ask the questions in some cases. And it’s just been wonderful. I’ve become an advocate for Moffitt. I talk to people in the community. I go to Tallahassee with a group of people and talk to our legislatures about funding for Moffitt. I’m participating in the Miles for Moffitt next month as a volunteer. Not as a runner, but as a volunteer, to help raise money for Moffitt to find if not the cure at least the way to extend someone’s life with good quality.

Andrew Schorr:   

Wow.

Edward Cutler:     

And I thank you all for that.

Andrew Schorr:   

We wish you all the best. I wanna say to our audience that could be anywhere in the world, I think the lesson of what Ed is saying is go to a center where they’re knowledgeable to at least get a second opinion, Dr. Boyle had mentioned that earlier, and connect with a team like this. And then when they help you and you’re given higher quality of life hopefully and longer life, then go to bat for other people. Whether it’s with your center, like Ed has, or in a state, speak out because you can help a lot of other people. I try to do that too.

Edward Cutler:     

One other thing, Andrew. I have another thank you. Well, it’s actually two other thank yous. First to my wife for being a great support. And second, to the man who had the vision to make Moffitt reality. And that is H. Lee Moffitt who at one point in time was the speaker of the house of the Florida legislature. It was his vision. Unfortunately, he had cancer and that generated his vision. But he’s still going strong and he’s still working very hard for this institution.

Andrew Schorr:   

Well, I wanna mention then lastly that we can all make a difference. The doctors making difference, patients, family members in that collaboration and in helping others. I wanna thank everybody for being with us today. I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

What Is the Value of Diversity in Clinical Trials?

Clinical Trial Mythbusters

Clinical Trial MythBusters: What Is the Value of Diversity in Clinical Trials? from Patient Empowerment Network on Vimeo.

Downloadable Program Guide

In this MythBusters program, Senior Vice President and Chief Medical Officer (CMO) of ASCO, Dr. Robert Schilsky, and 20+ year CML survivor, Mel Mann along with Cecelia Mann, will unpack some of the issues that have led to the lack of diversity in clinical trials and initiatives in place that are changing all of this.


Transcript:

Andrew Schorr:
And greetings from near San Diego, Carlsbad, California. I’m Andrew Schorr from Patient Power. Welcome to this Patient Empowerment Network program, the next in our series Clinical Trial Mythbusters, and this program is so important, discussing what is the value of diversity in clinical trials. And, believe me, you’ll hear it is so critical. We have to do better, and we’re going to discuss that over the next hour.

I want to thank the companies that have provided educational support through grants to the Patient Empowerment Network. They have no editorial control, but their support is welcome. And that is AbbVie Incorporated, Astellas, Celgene and Novartis. All right.

We’ve got a lot to discuss today, and we welcome your questions along the way. I want to first introduce someone who, like me, has greatly benefited from a clinical trial and believes that they are alive today because of their participation. And so joining us from Atlanta is Mel Mann along with his wife and care partner Cecelia Mann. Mel, welcome to the Patient Empowerment Network program.

Mel Mann:
Thank you very much.

Andrew Schorr:
And we’re going to hear more of Mel’s story in just a minute. I want to introduce a very prominent medical expert who joins us. He is the senior vice president and chief medical officer at really the largest cancer organization, the American Society of Clinical Oncology, and that is Dr. Richard Schilsky. Dr. Schilsky, welcome to our program.

Dr. Schilsky:
Thank you, Andrew. Happy to join you.

Andrew Schorr:
Okay. And are you in the Washington, DC, Virginia area?

Dr. Schilsky:
That’s where our organization is based, in Alexandria, Virginia, yes.

Andrew Schorr:
Thank you for being with us. I should mention that Dr. Schilsky has had a lot of experience related to trials. He was the head of hematology/oncology at the University of Chicago, which of course Chicago is a very diverse city, and the University of Chicago does a lot of research. And he also helped run a big research group that doctors from around the world are part of, and he did that for many years. So we’re going hear more from Dr. Schilsky in just a minute. But, first, Mel. So Mel, in the late ’90s you were dying, right, of chronic myeloid leukemia, correct?

Mel Mann:
Yes, I was.

Andrew Schorr:
Losing weight and being told that there wasn’t much to do, right?

Mel Mann:
Correct, yes.

Andrew Schorr:
Maybe a transplant. But you were in Atlanta and you went from doctor to doctor, but somehow you got to MD Anderson, a major research center in Houston. What did they offer you there?

Mel Mann:
When I first went out to MD Anderson they said they were going to put me on a clinical trial after clinical trial. And the first thing they did was increase my dose of interferon, and that was the medication, the standard therapy at the time, and then they tried different combinations of drugs, and eventually I started on different clinical trials.

Andrew Schorr:
Okay. And, Cecelia, you were there in Atlanta and he was scooting over to Houston, it’s not exactly around the corner. Why were you supportive of that?

Cecelia Mann:
I was supportive of that because that was the last chance that he had to a cure and for survival. So from the very beginning, whatever type of treatment he needed when he was flying around, whether he was going looking for bone marrow transplants, doing bone marrow drives, and therefore I was supportive of. We had a five‑year‑old daughter at the time, and so anything that Mel needed I was there to support him.

Andrew Schorr:
So, Mel, this is a happy story because here we are in 2018 as we do this program and you are with us when many people with CML at the time were not with us that long. Hopefully, a transplant could be curative, but a lot of people passed away. You were lucky enough to come back as they were rolling through different trials and there was a new one that opened up for a drug called Gleevec, a pill.

Mel Mann:
Yes.

Andrew Schorr:
What happened?

Mel Mann:
Okay. So in the summer of ’98 the Phase 1 Gleevec study opened up, and I went out to MD Anderson, and I was patient number two, and I started taking it at a low dose, and it was effective for me. And eventually they increased the dose and it started changing my leukemia around to eventually I reached what they call a major molecular response. And that was 20 years ago. This summer I went over 20 years.

Andrew Schorr:
Wow. Well, Dr. Schilsky, is that an example of a patient getting, if you will, tomorrow’s medicine today, what we hope for?

Dr. Schilsky:
Absolutely. And, first of all, it’s such a wonderful story, Mel. It’s great to hear you tell it, and it’s exactly why we do research, exactly why we do clinical trials, to try to discover the new therapies that people need that will give them the kind of long‑term survival and quality of life that you’ve been experiencing. It’s just‑‑it’s wonderful.

Andrew Schorr:
So, Dr. Schilsky, let’s get into the problem. So, generally, there are many clinical trials that take longer than one would hope to fill, and the FDA and I know scientists have been seeing well, gee, how do we know what we’re testing applies to people maybe with different ethnic, gender backgrounds, a variety of situations, and often we can’t find people who fit those categories to be in. What is that‑‑how poorly have we been doing in the past with diversity in trials, and what does that mean for developing new medicines?

Dr. Schilsky:
Well, we don’t do well in almost any dimension. We don’t get enough underrepresented minorities in clinical trials. We don’t get enough older people in clinical trials. You have to remember that 60 percent of cancers occur in people 65 years and older, and yet only about 10 percent of people participating in clinical trials are 65 and older. So we are having to treat the majority of older people, and I would say the majority of minority people, with data derived from participants in clinical trials who are not like them.

We need to change that for a whole host of reasons. It’s historically been very challenging, and the problems really sort of boil down into three big areas that I think we can discuss a little bit further.

First is awareness. Many people are not aware that clinical trials are even an option for them. Many people think that a clinical trial is a last resort, and I want to dispel that myth right out of the box. Clinical trials can be a very good option for patients right from the time of their cancer diagnosis even if it’s their very first treatment. So clinical trials may be a last resort, but they don’t have to be, and there are many clinical trials that are appropriate for people right following the initial diagnosis of their cancer.

So there’s the awareness issue, and sometimes, frankly, not even the doctors are aware of what clinical trial options are for their patients. And the one thing we know for sure is that the most influential person as to whether or not a patient goes into a clinical trial is their doctor. If the doctor does not recommend it, if the doctor is not aware of it, it’s not going to happen.

But then you get into the more technical issues. There are things, there are rules for clinical trials because they are research studies. They are experiments. There are very well defined rules, most of which are in place to protect the people who are participating in the study. Some of these rules are called eligibility criteria, and they specify the characteristics of people who can enroll in the study. Well, historically, they tend to be very rigid and very limiting, and you’ll often hear people talk about how the only people who can get into clinical trials are Olympic athletes. That may be the case, but it’s not Olympic athletes that we’re treating in the clinic every day, so we need to make our clinical trials more representative so that they’re more applicable to the typical person that a doctor sees in their office.

And then there are the logistical or operational issues of the clinical trial. The clinical trial can be very burdensome. Mel just described how he had to travel from his home in Atlanta to Houston to participate in a clinical trial. Not everybody can afford to do that. Not everybody can take time away from work, time away from home. And the clinical trial requires not only that you travel sometimes but that you travel on a specific schedule because of the requirements of the trial.

So all of these are issues that are‑‑can limit participation in trials, and many of them are magnified in minority populations or in populations that don’t have the economic resources to be able to meet the requirements of the trial.

Andrew Schorr:
Right. Let’s talk about that for a minute. So, Cecelia, you go out in the community and speak to people, and you probably meet some people who maybe are diagnosed with a blood cancer, like you’re active with the Leukemia and Lymphoma Society so you may speak to them, and they say even if you brought up about a trial, they say, hey, Cecelia, I’m working two jobs. Or my husband or spouse is working two jobs, and we’ve got two kids, three kids. How could we ever participate? We just can’t get away or we don’t have the family support or whatever. Those are real issues, right?

Cecelia Mann:
True. True, those are real issues, and I try to direct them towards resources that Mel and I found out about along the way. The Leukemia and Lymphoma Society, they have resources to help with travel, and American Cancer Society has resources that help with the hotel and lodging. And there are a number of other different types of funds that can be assessed to make that a possibility.

But you’re right, Andrew. I had one young lady at a health fair and a second cancer had popped up, and she was coming there to get information, and she was saying that they were saying it wasn’t too much they could do, and I brought up MD Anderson. And she immediately said, I can’t go out there, I have to go to work, and she turned around rough. And so when they listen to me then always glad to tell them about it and let them know there is an option and that clinical trials work, and I point to Mel, my husband, as a success story also.

Andrew Schorr:
So, Dr. Schilsky, you talked about physician awareness. It’s also about more physicians participating in trials at I think what you call the community level. So, in other words, MD Anderson and where you work, at the University of Chicago, those are big city centers and where they are in Atlanta there’s Emory and some other mainly centers, but what about out in the hinterland, if you will? Can somebody who lives there diagnosed with a cancer, how do they have access to a trial that their doctor knows about and maybe that’s more close to home, if you will?

Dr. Schilsky:
Right. So of course we know that anybody with cancer prefers to be treated in their community, and most are. So one of the goals is to be sure that oncologists practicing in all sorts of community settings have access to clinical trials. Now, one of the ways that happens is that for more than 50 years now the National Cancer Institute has actually been operating and funding a community‑based clinical trials network. It used to be called the CCOP program. That’s an acronym that we don’t have to go into. They’ve recently changed the name. It’s now called NCORP program, but‑‑that stands for, I think, the National Community Oncology Research Program.

But the point is that the program, which is in most but not all of the states in the United States, funds community oncologists to participate in NCI‑sponsored clinical trials, and there are at least 65 or 70 such clinical facilities around the country right now. So in those medical practices patients can find those clinical trials in their communities without having to travel.

There are also other community‑based networks that are active participants in cancer clinical trials. So I think at the end of the day the critical thing for patients, and this is sometimes easily forgotten because you’re so, you know, your thinking and your time and your emotion are all taken up in dealing with the cancer diagnosis. It’s really important, though, to ask the doctor, do they have access to clinical trials. Do they have a clinical trial that might be appropriate for you? And if not you might want to consider where else you could go, hopefully still relatively nearby to get access to a clinical trial.

Andrew Schorr:
Mel, so for you, you went around to some doctors who were not aware of anything new to do for you, right? And that’s still true in so many areas of cancer. Now, what do you say to patients about speaking up because Dr. Schilsky just referred to it, people are terrified. They really just want the doctor to have the answer. What do you tell people so that they maybe advocate for themselves?

Mel Mann:
Okay. So if you’re looking for a clinical trial and I’m out at, like you say, a health fair, we have a‑‑the Leukemia and Lymphoma Society has something called the clinical trial support center, and they have nurses who work early in the morning till late at night. And you call them up and you tell them about your illness, and they check the availability for what clinical trials are out there, and then they narrow it down to what you actually qualify for, and then they take into consideration your finances and other issues.

And then you’re left with a number of possible clinical trials that you have, and you can take that back to the doctor and you can discuss that with him. So that’s one of the things I talk with them about.

Andrew Schorr:
I could mention, now this is really more broadly across cancer, too. So there are breast cancer groups, there are lung cancer groups, and I would just make a pitch to find out, is there a local chapter or national number for you, for the cancer you or a loved one been diagnosed with, and that’s the question.

Mel Mann:
Yes.

Andrew Schorr:
Say, look, A, I don’t want to feel I’m alone, and, B, how do I get‑‑how do I get connected with what could be lifesaving or life‑extending treatments for me and that I could discuss with my doctor. And understanding‑‑and then, boy, if there are obstacles like financial issues, logistical issues, travel issue, is there support for that.

Mel Mann:
Yes.

Andrew Schorr:
So let’s go back to the inclusion/exclusion or eligibility issue you spoke about, Dr. Schilsky, because, you know, somebody who has cancer may also have heart problems or diabetes or some other issue. Maybe they previously had another cancer, and so for the companies developing new drugs they may be happy with narrow inclusion criteria because they don’t want to have anything get in the way, some previous thing you’ve had, to affect their ability to have a new drug go on the market.

So what kind of work is going on between government and the drug manufacturers so that the criteria, not so tight, but you can still get legitimate scientific answers?

Dr. Schilsky:
Right. So, as you alluded to, Andrew, there are good reasons that there are eligibility criteria. One of them is to protect the patients in the study from circumstances that would increase their risk of participating in the study. Another is because the companies or whoever is sponsoring the study wants to be able to isolate the specific effect of what they’re studying without having a lot of confounding factors that could muddy the water and makes it difficult to interpret the results. But that said, the bad thing about all that is that the results of the study might not be applicable to the majority of people who could benefit from the treatment because they weren’t included in the study to begin with.

So one of the things that my organizations has been working on very hard over the last couple of years now, and we’ve been doing this collaboratively with people from the Food and Drug Administration and the National Cancer Institute and a lot of clinical experts and a patient advocacy group, Friends of Cancer Research, is to try to expand or broaden or simplify some of these eligibility criteria that tend to keep people off of trials and in particular tend to keep minority populations off of clinical trials.

So, for example, it’s not unusual for someone who has a new diagnosis of cancer to have previously had some kind of cancer earlier in their lives. So we might see a patient who has lung cancer who 15 years ago had a diagnosis of prostate cancer. Well, for that lung cancer patient to go on a trial that has the typical inclusion and exclusion criteria that doesn’t allow for this previous malignancy, they would be excluded even if they had been cured of that prostate cancer 15 years ago.

We also see, and you mention what we call in the medical profession comorbidity. So if someone’s got cancer and they also have heart disease, they also have diabetes, high blood pressure, anything that affects the functioning of your normal organs, can also exclude people from participating in trials, and there are certain limits that we feel can be expanded and still allow the treatment to be given safely.

So just about a year ago now we came out with a set of recommendations for how eligibility criteria can be modified to make clinical trials more inclusive. And now just recently, I’m really pleased to say, the National Cancer Institute expanded their sort of template protocol document that many investigators follow to incorporate our recommendations, so now their standard protocol includes these broader inclusion and exclusion criteria. And the FDA now is working on what they call guidance documents to advise commercial companies that are running clinical trials to do just the same thing. So we are very optimistic now that we’ve got this ball rolling. We’re going to be removing these obstacles, and we’re going to be able to have more inclusive and diverse population of patients who participate in cancer clinical trials.

Andrew Schorr:
Great leadership. I hope it works great, and we’ll be happy to support you. So, Mel and Cecelia, let’s talk about the money part of it a little bit. So you were making trips to Houston, Mel, Cecelia was home with a five‑year‑old, and so admittedly there may be hardships, financial hardships, being away from family if you have to go to a trial somewhere else, checking back. What do you say to people when they say, well, I’m just going to go with the traditional stuff. It’s close to home. In other words, if there can be programs that can help them it still takes courage, if you will. So what would you say to people about investing in their life, if you will?

Mel Mann:
Well, you know what the standard, what the current treatment is and the outcome of that, so if you want to have a different outcome then you have to try something new which is probably going to be a new drug. So you have to weigh that with the cost and the travel. Some people may not have the support, the caregiver support to go a long distance, so you have to take that into consideration. As far as the Leukemia and Lymphoma Society they do have certain funds where they can help with travel pay, co‑pay, insurance premiums, that could help alleviate some of it. So there’s a lot of stuff that’s involved, and it’s an individual decision.

Andrew Schorr:
So we’ll just make a comment, though. So, many people have a church or synagogue, friends, neighbors even if they’re living alone, but yet people are sometimes hesitant to ask for help. And I would say speak up. People do want to help you.

Dr. Schilsky, let’s talk about another reality of trials. There’s a history certainly and some fear still in the black community of whether they were tested on, without their knowledge even, going back years and the general thought, you’ve heard it through your career, I’m sure, people say, well, I don’t want to be a guinea pig for a couple reasons. One is we don’t know if it’s going to work. And second of all if there are different arms of a trial I don’t know if I’m going‑‑I’m going to go to all this trouble and expense, I don’t know if I’m going to get the good stuff. So maybe you could speak about that a little bit. First of all, the fears of being experimented on, and then also about whether you will get what could be a breakthrough.

Dr. Schilsky:
Yeah. Well, for sure, you know, there is this sort of sordid history of inappropriate experimentation on people, and clinical trials are a form of experimentation. They are a form of research. There’s no doubt about that. But clinical trials these days are highly regulated, overseen by independent groups that include patients and clinical experts that come together in committees called IRBs, Institutional Review Boards, and they evaluate on both the risks and the benefits to patients who participate in clinical trials.

They make sure that the trial has an appropriate consent process associated with it, that it’s explained in plain language to patients, so I think these days a lot of those concerns no longer exist. And I hope that people can get beyond the history that led to some of those concerns. The‑‑sorry, I lost a train of thought on the rest of your question.

Andrew Schorr:
The issue about are you going to get the good stuff.

Dr. Schilsky:
Oh, yes. So a couple points there. One point I want to make clearly is that in most cases cancer clinical trials do not include a placebo or an inactive treatment. That’s not always the case, but it’s true most of the time. So patients are always going to get at least the standard of care treatment, and of course the standard of care is what is at that time known to be the best available treatment.

The whole point of doing the research is to determine if the new thing is better, and of course we always hope it will be. It’s not always better, but sometimes it is, as in Mel’s experience. And I think this has to be clearly laid out to patients. They have to clearly understand why the research is being done. In many trials nowadays even if the patient is assigned to get the standard of care treatment there still may be an option to get the new treatment at a later point. So if the standard of care doesn’t work many times there’s still the opportunity to get the new treatment following the standard of care treatment.

So the trial really boils down to not standard versus new but new versus standard followed by new. So eventually everybody may have a chance to get the new treatment. That’s not always the case, but I think the key‑‑my key take‑home, in a sense, is that we’re doing the research because we think and we hope the new treatment is better, but we have to do the research to prove that. And everybody in a clinical trial I think can be assured that they’re going to get, at the very least, the best available standard treatment.

Andrew Schorr:
Mel, when you signed the papers to be in a trial, and you probably shared them with Cecelia, especially back in the late ’90s and I participated in one trial in 2000 and another in 2011, there’s a lot of paperwork, things in bold face written by lawyers. I didn’t always understand it. What propelled you beyond that? Was it just that, oh, my god, if I don’t get something I’m going to die? Or how did you two deal with the paperwork and feel comfortable signing on the dotted line?

Mel Mann:
Well, I saw a lot of hope in the paperwork. For example, one trial I was on was peginterferon, and I had been taking interferon every day, injecting myself, and I had to keep it refrigerated and when I travelled it made it difficult. So with peg I can take one shot a week, so that would make the cancer journey easier. It may not make me live longer, but it will improve my quality of life, so I saw my quality of life improving with that clinical trial. And I looked at the paperwork, and I went through it, and I felt comfortable with it.

Andrew Schorr:
And how about you, Cecelia? I mean, your husband says, well, I’m going to be in a trial and I’ve got to sign all these papers. Did you say at any point, wait a minute, that’s scary?

Cecelia Mann:
Well, no, I didn’t. I didn’t because with Mel, he had three years to find a marrow match, and he was at the end of year two and no match in sight. And so when he had the opportunity to go out to MD Anderson and be on a clinical trial or several, I was okay with that. I was okay with that. And I looked at it as actually being a blessing. And it turned out to be, and we’re grateful.

But I would say to anyone else who is contemplating a trial and that person and their caregiver, their spouse, to just educate yourself, and get as much information as you can, ask as many questions as you can, but please don’t just throw it away out of hand. It’s definitely worth considering.

Andrew Schorr:
Dr. Schilsky, so we have more than 50 million people with a Hispanic background in the United States, and even if many people are speaking English they may speak Spanish at home. And then when you are diagnosed with a cancer there’s a whole new language of stuff that comes into play that even if you’re fluent in English it may not be either what you easily understand or even aligns‑‑what’s being asked of you aligns with your cultural background. Okay? So how, beyond, let’s say, the African‑American community, when you look at the Hispanic community, how do we encourage participation there and get over some of these cultural or language nuances, if you will?

Dr. Schilsky:
Yeah. So it’s much the same thing in the sense that the same information has to be conveyed but it may have different meaning and different interpretations in different ethnic and cultural groups. Most clinical trials now will have a consent form that is fully translated into Spanish. But, of course, there are many different languages on the globe. When I was practicing at the University of Chicago for many years on the south side of Chicago, we had Polish‑speaking people, we had Russian‑speaking people, we had people‑‑Chinese‑speaking people.

So the requirements actually are that there must be a consent form, at least some reversion of which is translated into the first language of the patient. So if you’re a native Spanish speaker, a native Chinese speaker, you have to have, be able to see a consent form written in that language, and generally speaking you have to have your native language interpreter present in the room to help you go through the consent form and respond to your questions. And that person has to be someone who is independent from the research team so they can give you the straight answer and not be influenced by any member of the research team. So I think all of that certainly helps.

But, again, what helps a lot more is to have members of the care team who look like the patient. So we have problems with diversity in our profession as well. We have very few African‑American oncologists. We have more Spanish‑speaking oncologists, but again we have few Asian oncologists. So we need to do a better job of improving the diversity of our profession, improving the diversity of the care teams. We need nursing staff and research staff and other people who work with our patients who represent them and gain their trust, who look like them, who talk their language. And I think that will go a long way toward making people feel more comfortable about participating in clinical trials.

Andrew Schorr:
I was at a conference last week and I heard some of the patient experience, people from different drug companies talking about how they were trying to simplify their forms because I know in 2000 when I entered a Phase 2 trial there were all kinds of black boxes, you could die, you could this, everything in the kitchen sink was in it. I’m still here, and I think because of the trial, and most of the side effects I didn’t have or they were definitely handled extremely well.

So right now, where are we, Dr. Schilsky, with participation? And why is it important? In other words, in this age of personalized medicine why do we need more black people in certain trials? Like, I know in multiple myeloma, one of the areas we cover, there’s a higher incidence in the black population, right, but yet few black people are in the trials for myeloma drugs. Or maybe there are differences with Asian populations or other populations. So is it that you can’t really get a clear scientific answer on the differences? Is that it?

Dr. Schilsky:
That’s part of it. First of all, we want anybody who could potentially benefit from being in a trial to be able to be in the trial for their own personal benefit. Secondly, we need to learn about the performance of the drug or the intervention in all the diverse populations in which it might be used. And one of the things we have learned is that not all populations respond the same way. Some treatments are more toxic in certain racial or ethnic groups. Some are more effective in some racial or ethnic groups.

And, you know, since you brought up this whole new world of precision medicine, I’ll give you the example of the lung cancer drugs that are used to treat the specific mutations in a gene called EGFR. So that’s a gene which has mutated in about 15 percent of Caucasian patients with lung cancer, but it’s mutated much more commonly in Asian patients. And in fact one of the clues that there was even a gene mutation that was important in determining whether these drugs worked or not was because it was observed that the drugs worked better in the Asian patients in the clinical trials even before the genetic abnormality had been discovered. And the clue was what’s different about the Asian patients than the other patients in the trial.

So the diversity is critical to our learning and critical to our application of the therapy in all the diverse populations that we serve.

Andrew Schorr:
If you’re in our viewing community and you have a question, send your questions into questions@patientpower.info, questions@patientpower.info. We’ll continue our discussion of course, but we invite you to join in.

So, Mel, when you get to talk to people, what do you say? Somebody is sick, diagnosed with a cancer, what do you say? Dr. Schilsky was talking about not seeing clinical trials as a last resort, and you weren’t seeing it that way (?) Inaudible, but today what would you say to people when you talk to them about it?

Mel Mann:
Well, I will say explore your possibilities because there are all different opportunities at each phase. You may not go into Phase 1 but you could do a Phase 2, 3, 4‑‑or Phase 3, and you don’t know what’s going to happen in each of those phases. So you just have to see what’s out there. And I’m exhibit A, so they look at me and they say, well, I can work, and then not as suspicious, you know. We have Tuskegee, and that was 1972, and it was that dark period of cancer history so that kind of rolls around in their mind, but you can’t let that jeopardize the opportunity such as Gleevec that I took advantage of. So we know that Gleevec worked, and there are other drugs that have improved the quality of life and the lifespan of cancer patients. So definitely research those drugs.

Andrew Schorr:
Did you lose heart when you were first in one trial and the medicine wasn’t working for very long? Some would say, well, all right, I tried a trial, forget about it, you know. But you then pursued other trials. What propelled you to do that?

Mel Mann:
Well, I was still in the game, so I saw that these trials took‑‑well, first of all, I could not find a bone marrow donor, but a bone marrow transplant was pretty drastic in itself so I was looking at these other opportunities as maybe not even having to take part in‑‑have a bone marrow transplant. So that was another incentive. So‑‑and I knew that if I didn’t find one‑‑there was a very small chance, there was only about 5 percent of Americas who are on the marrow registry, so basically I was helping to build a list, maybe not for myself but for people in the future who needed a transplant.

Andrew Schorr:
Dr. Schilsky, let’s talk about the pace of research. So, first of all, if we don’t get enough participation in trials how does that slow drug development?

Dr. Schilsky:
Well, it slows it down enormously because we have to have a certain number of people in each trial to be able to get a reliable answer. And these days it’s becoming even more challenging because as we’re developing drugs that only target a specific genetic abnormality in the tumor which sometimes is very rare so we may be looking for a genetic abnormality that only occurs in 2 or 3 percent of all people with a certain kind of cancer. First you have to find the people who have that genetic abnormalities, then you have to be able to enroll them in a clinical trial. They have to be willing. They have to meet the enrollment criteria. So it can take a long time, and even a global effort to find enough people to fill out a clinical trial.

And most clinical trials in order to produce a reliable result are going to require a minimum of 50 to 100 patients. Some require many hundreds of patients or even many thousands of patients depending on the question being asked. So you can see if people are not participating it’s going to take long time to get those answers.

Andrew Schorr:
Now, Mel, you got Gleevec in a trial at least three years before it was approved, and it was approved fast because it was such a breakthrough, right? So you literally got tomorrow’s medicine today, and it saved your life in the process, right?

Mel Mann:
Yes, because I was past the three years. I was about three years and eight months in my diagnosis, so you add another three years onto that and I would not have been here.

Andrew Schorr:
Right. In my case I was in a trial related to chronic lymphocytic leukemia, three‑drug combination, and I received that in a Phase 2 trial 10 years before that was approved. So it was a long time.

So I have a question for you about personalized medicine, Dr. Schilsky. So for instance in chronic lymphocytic leukemia I’m not‑‑I’m Caucasian but I’m Ashkenazic Jewish, okay? So where we’re going with personalized medicine, are we beginning to find subsets among Caucasians, among African‑Americans, among Asians, where there are even more narrow slices to help us understand targeting of medicines and what’s effective for whom? Is that where we’re headed?

Dr. Schilsky:
Absolutely. And, as I said earlier, we’re seeing that all the time. So almost every common cancer now is being broken down into a whole basketful of rare cancers under the broad umbrella of whatever the cancer type. So lung cancer, there’s probably six or eight different kinds of lung cancer now that each have a specific genetic abnormality, that each requires a specific treatment. And many of those treatments now are FDA approved, but the first thing you have to know is does the cancer have the genetic abnormality and then what is the appropriate treatment to use. We’re seeing that in breast cancer, in melanoma, in many other kinds of cancer types.

There’s another‑‑there’s a related issue here, though, of course, which is that not everybody metabolizes drugs the same way, and so another reason to have diverse populations in a clinical trial is to learn about side effect profile of the drug, learn about the right dose of the drug to use. And we know full well, for example, that African‑Americans metabolize some drugs differently from white people, and so, depending upon how the drug is working in the body, an African‑American person might require a higher dose or a lower dose of the same drug that a white person would require in order to get the same therapeutic effect.

So it just speaks to the point again where if you don’t have diverse populations in the trials you can’t learn this stuff so that doctors then have the information they need to be able to prescribe the drug in the best way for their particular patient.

Andrew Schorr:
Okay. Here’s some questions we’ve been getting in. Kaitlin wrote in, Mel, she wants to know, do you still participate in follow‑up activities related to the trial you were in? So tell us about your participation and sort of follow‑up.

Mel Mann:
My follow‑up is I go out to MD Anderson twice a year, and it’s just a one‑day, one‑hour doctor visit where they take the blood work and they check and see if everything’s stable. And then when I’m back home, twice a year I have my blood work checked back at home, and that’s the extent of the follow‑up. I still have to take medication, one pill a day.

Andrew Schorr:
Right. And is that still covered by the trial?

Mel Mann:
Well, it’s covered by the trial, but my insurance also covers it. I did Gleevec for life because of the trial.

Andrew Schorr:
Okay. Dr. Schilsky, let me just ask you, is that a benefit typically of trials? Like with these oral cancer medicines which you know can be so expensive, if you’re in a trial for one do you get it for life or an extended time or how does that work?

Dr. Schilsky:
Depends a little bit on the trial and the sponsor for the trial, but the one thing for sure is when you’re on a trial whatever the investigational drug is, whatever is being researched, that’s provided for free. And any testing that would be considered to be for research purposes is provided by free‑‑for free. So that’s a benefit of participating in the trial.

Typically the drugs continue to be provided for free for as long as the patient continues to benefit. Now, sometimes if the drug ultimately gets FDA approved then it may be necessary at some time in the future for a patient to switch over from the research drug to the commercial drug, but of course at that time the drug is FDA approved and if the person has insurance it will generally be covered by their insurance.

Andrew Schorr:
Okay. We got a question in though for you, Dr. Schilsky, from Darrell. We were talking about genomic testing to understand what version of a disease we have either because of our ethnic background or some other thing that’s going on with us. As you know, insurance companies for a while have been balking at some of these more sophisticated tests, yet we and our doctor need that for us to get what may be right on target for us. So maybe you could talk about work that ASCO’s doing at all related to that. We want the testing done, but we also want to get it paid for so we can get that right, precise care.

Dr. Schilsky:
Yeah. It’s a complicated question because the testing is done at different points in the person’s illness. And so typically a test on a tumor specimen that’s necessary to determine a standard of care treatment, and many of these tests are referred to as companion diagnostic tests. Those tests typically are covered by insurance because the treatments themselves are also covered by insurance and the only way to know if you can get the treatment is to have the test done.

Now, where it gets a little bit uncertain is when you get into this sort of large‑scale genomic testing where a patient’s tumor might be tested for many hundreds of genes not really knowing what you’re looking for and not really knowing what you’re going to do when you find it. And that is where you’re beginning to bump up a little bit against, research and that’s where the insurance companies, sometimes some are reluctant to pay for that kind of testing.

Now, at least one of those large genomic profiling tests earlier this year was approved by both the FDA and Medicare and now will be reimbursed. So that’s the good news, and I think that’s the direction that most insurance companies are heading in.

One of the things that my organization is doing to try to understand how best to use these tests and how best to use targeted cancer drugs is we’re doing our own clinical trial that’s available in 20 states around the country, so not the entire country yet, but has already enrolled more than 1200 people on the study over the last two and a half years. And we’re doing this study to understand how this kind of genomic testing is done, what kind of treatment is recommended based on the results of the genomic test and whether or not that treatment actually works.

Andrew Schorr:
Cecelia, you mentioned earlier about the lady walked into the health fair and when you started talking to her about trials she said I got to go to work, and she walked out. And Dr. Schilsky was talking about eligibility requirements, but there are other issues where the study may be asking you to come back to some place or have multiple tests with some frequency so it’s not just leaving work one time. It may be leaving work 20 times. Have you had people voice that concern to you, that it’s just‑‑what’s being requested is just too much?

Cecelia Mann:
Yes. I think the lack of convenience for people who don’t have the funds or don’t search out the funds would definitely hinder them being on a clinical trial or being open to hear about the clinical trial. So, yeah, convenience and awareness. We try to spread awareness that, yes, after we talk about the disease, the myeloma and the symptoms then we go into the resources. And, you know, I make sure I tell them about calling the information line and talking to the masters level oncologist professional there and finding out about the latest trials, the latest treatments in addition to what they’re doing currently with their doctors or their family members or friend that is diagnosed with one of the blood cancers.

Andrew Schorr:
Dr. Schilsky, she’s getting at helping people sort out what trials are available. So medical science is a moving forward, and I’m sure you as an oncologist say, hallelujah, there are more trials than ever, but it’s often not only daunting to understand any one of them but to go through a bunch of them to understand what might be right for you. So how can ASCO help that? Is it just simply educating your doctor, or what can we do for families affected by cancer so they can get at what could be a match for them?

Dr. Schilsky:
Yeah, it’s a great question. So there are a lot of resources available, as Cecelia has mentioned. We can help patients understand and even begin to sort of, you know, wade through and winnow down the potential clinical trial options for them. One things that we’re working on and very interested in doing is sort of flipping the current paradigm by which trials are done. So right now, typically speaking, the patient has to travel to whatever site has the trial available. If they’re fortunate enough that that’s their own doctor’s office, that’s great, but, as in Mel’s case he had to travel to MD Anderson to get the trial.

The technology these days is at a point where we think we can flip that. Instead of making the patient go to the trial we’re going to work toward making the trial come to the patient. So if your doctor is aware that a trial exists somewhere in the world it should be possible for the doctor to basically just go to a website, find the research study, find the consent form, find the other documents that are necessary and present that to the patient. And if the patient qualifies just sign them up instead of making the patient travel hundreds of miles away to the one place that has the trial available.

Some trials have already gone down this road, and they’ve actually been recruiting very successfully, but it’s still not the usual way in which things are done, and we think we need to try to flip things around a little bit to make it easier for the trial to come to the patients. Let the trial travel. Let’s not make the patient travel.

Andrew Schorr:
That sounds great.

Mel Mann:
Can I add something to that, Andrew?

Andrew Schorr:
Sure.

Mel Mann:
Okay. As a veteran, I was part of the VA system, and I had to go out to MD Anderson, but this summer they started something called Navigate, the VA had started something called Navigate, which partners with the NCI. And it’s at 12 sites around the country, and it’s to bring the clinical trials to the VA. It’s right there. So if it’s an NCI clinical trial then the veteran can get on that clinical trial. And there’s a lot of African‑American veterans who can take advantage of that.

Andrew Schorr:
For sure. That’s terrific. So we’re going in the right direction. One other thing I think that needs to change is we talked about the scientists, whether they’re federal government scientists or drug company scientists, and they want to get answers to a whole bunch of scientific questions. So they may say, as you write the protocol I think it is, well, you have to get so many CT scans and you have to get so many blood tests and stuff like that. And it can become onerous, Dr. Schilsky.

What’s happening in trial design so that, A, we talked about eligibility, you can get into the trial, but the things you’re asking of me may have logistical hurdles as well that you’re kind the lightening up on it to get to the key scientific question without all these other bells and whistles that make it tough on me.

Dr. Schilsky:
Yes. I like to think of it as the need to know and the nice to know, right? There are certain things you need to know in the trial to be sure that the treatment is working, the patient is safe and not having any severe side effects and things of that sort. A lot of that stuff is the same stuff that doctors order every day on their patients as part of routine clinical care, and so much of what needs to be collected in clinical trials really aligns pretty well with standard of care.

Now, that said, because clinical trials are research and because there’s always new frontiers to explore, sometimes testing in a clinical trial extends beyond what the standard of care is. Sometimes patients are asked to give extra specimens of their blood, of their normal tissues, of their tumor tissues. Extra biopsies might be required, things of that sort. Patients need to understand why they’re being asked to do that, what those specimens are going to be used for, how is it going to advance research.

And, frankly, they’re very important to expanding the scope of the research. So, for example, oftentimes those specimens are used. If the treatment doesn’t work in a patient having those specimens can help the scientists understand why the treatment didn’t work, and that opens up a whole new horizon to explore to potentially make the treatment better in other patients.

Andrew Schorr:
Mel, do you recognize that by being in a trial and the work that you and Cecelia have been doing that you’ve probably helped thousands of patients by first being in a trial and then you and Cecelia talking about it?

Mel Mann:
Yeah. Yeah. I guess that’s kind of hard sometimes. You don’t see yourself in that role, but as I look back on it, yes.

Andrew Schorr:
Cecelia, you’ve probably talked to a lot of people. Have you seen a change where‑‑you’ve been doing this for a number of years where earlier on people said no, no, no. Are people more receptive? Do you see a change going on? Let’s say in the African‑American community, do you think people are a little more receptive?

Cecelia Mann:
Yes, I think so. I think they are more receptive, and this has a lot to do with education and awareness, and that’s what we are out there doing when we are out there in the community. And the more they hear about it and the more they read about it and the more they can see examples like Melvin, and we know one or two other people that we’ve met that were also on a clinical trial. One is in our church, and he had a type of leukemia, and we didn’t know why he was sick. But he is doing very well.

And so the more we can get those examples out there in the community of successful clinical trial patients, it really helps and goes a long way toward helping people of color relax and come aboard. And I just say, please, do your research, educate yourself and ask questions and please stay open and don’t dismiss clinical trials out of hand.

Dr. Schilsky:
And, Andrew, if I could just add to that. I just want to make the point that it’s people like Mel who are creating the future. Everything we know about how to treat cancer we learned from the people who participated in the clinical trials. We’ve been doing clinical trials in cancer for at least 70 years, and all of the standard of care treatments that we have today came from the participation of people in clinical trials. And that’s how we make progress. That’s how we’ll continue to make progress.

So it’s the clinical trial participants who, sure, they’re in it for themselves. We understand that. They’re looking for a new treatment, a better outcome, but they are the heroes of oncology because they are paving the way, trying the course and ultimately making a better future for every cancer patient who follows them.

Andrew Schorr:
Amen. Let me just recap a couple of things, and correct me if I get anything wrong, either of you. So, first of all, Dr. Schilsky, I know there are more trials now than ever before, and they’re now looking at these rare subtypes as well, and so if we participate we may get the benefit of tomorrow’s benefit today. Cecelia was talking about assistance programs, people to help you sort it out, that you are noticing how there are difference among us about the ways that drugs are effective or not, and that’s so important to learn.

If we partner with you, Dr. Schilsky, and the many thousands of oncologists and researchers that you represent, can we get to the goal line faster? In other words, are you hopeful that if we really consider trials and participate in trials and stay in trials and the different groups that we can get closer to cancer cures?

Dr. Schilsky:
Absolutely. I mean, we have more and better cancer treatments today than we’ve ever had before. We have all sorts of new and hopeful treatments on the horizon. We have to prove that they are safe and effective treatments to get them out there into routine clinical practice, and that’s where the clinical trials come in. So the more people who participate in trials the more quickly those trials can be completed and give us an answer, then the more quickly those drugs will make their way into standard clinical practice where everybody can benefit from them.

Andrew Schorr:
Okay. So a couple of to‑dos for our audience if you’re a patient or a loved one or however you hear this. Ask your doctor about whether trials apply to you or your loved one who is diagnosed with cancer even if it’s on day one. You don’t have to be at death’s door. You’ve been diagnosed or a diagnosis is suspected, what tests can we do, how do we know what we’re dealing with, and when we look at the treatment options is a trial a possibility if that makes sense, right?

Dr. Schilsky:
Absolutely.

Andrew Schorr:
Okay. Step two, are there resources to help me overcome any obstacles I may have to participation, first understanding the trial, understanding it in my first language, sorting out is it right for me, getting to where it is and then staying in the trial because many people, unfortunately, don’t stay in the trial and so how do be help the trial get to the goal line?

And then lastly, Dr. Schilsky, it sounds like you’re doing a lot at the community level to have more doctors have an easier time of the bureaucracy that we’ve had with trials before and the understanding of this flood of trials that’s happening, right?

Dr. Schilsky:
Absolutely. And, you know, to be perfectly honest, the clinical trial community has‑‑we ourselves have created some of the bureaucracy, some of the excess regulation, some of the barriers to participation. It’s up to us to strip those away and solve the problem and make clinical trials more broadly available. We are working very hard now to make that happen.

Andrew Schorr:
Okay. So whatever community you’re in. I’m in the Ashkenazic Jewish community. Mel and Cecelia are in the African‑American community. We have people watching who are in the Hispanic community, the Asian community. If you have benefited from a trial, talk it up, right? Cecelia, people should talk it up, correct?

Cecelia Mann:
Exactly, yes. Please, talk it up.

Mel Mann:
Yes.

Andrew Schorr:
Mel, thank you. I wish you really continued good health. How many years has it been since you were diagnosed?

Mel Mann:
Well, in about two months it will be 24 years.

Andrew Schorr:
Twenty‑four years, and for me it’s 22 years. And had there not been trials either that we were in or somebody else was in we wouldn’t be here.

Mel Mann:
Yes.

Andrew Schorr:
So, thank you. And also, Cecelia, thank you for being a community activist when it comes to trials and being supportive of Mel as he’s been in a trial because some other people would say, you can’t go there, you can’t do this, and you’ve been supportive every step of the way. Thank you for that.

Cecelia Mann:
Oh, you’re so welcome. It was a pleasure to do it.

Andrew Schorr:
Mel and Cecelia Mann from Atlanta. And Dr. Richard Schilsky, you’ve devoted your life to this, Dr. Schilsky, and I just want to say on behalf of the cancer patient community thank you and thank you for the leadership that ASCO is trying to do, both with changing research requirements, working with government, working with industry, and you thank you personally for your devotion to us. I really appreciate you being with us.

Dr. Schilsky:
It was my great pleasure. And, again, congratulations to Mel and Cecelia.

Andrew Schorr:
Okay. Thank you all. So this is what we do with our Clinical Trials Mythbusters program. Please tell others about it. The replay is available very shortly and all kinds of little highlights that we’ve done today. But what’s important is wherever you are is remember we can’t develop new medicines unless all of us work together to participate to get the scientific answers that apply to us, whatever our unique situation is, and then we can work with government to approve new medicines, get them on the market and so many people can benefit in the US and worldwide.

Thank you so much for being with us on this Patient Empowerment Network program. I’m gratified to be part of it. Thanks too to our financial supporters AbbVie, Astellas, Celgene and Novartis and their dedication to drug development and supporting and sponsoring clinical trials. I’m Andrew Schorr near San Diego. Remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

How Cancer Can Affect Your Dental Health

More than one-third of all cancer patients develop complications or side effects that can affect the mouth, according to the National Institute of Dental and Craniofacial Research. While it is probably one of the last things you want to think about when faced with a cancer diagnosis, assessing your dental health and developing an action plan for how you will care for and protect your teeth and gums is a great way to ensure you don’t experience complications that can affect your treatment and general health.

Assessing Your Dental Health

The American Dental Association recommends treating areas of concern before you engage in any cancer treatment as it may help reduce possible side effects associated with chemotherapy and radiation. If you are able to do this beforehand, you will be able to address any issues such as cavities, gum disease or other dental hygiene issues that have the possibility of getting worse as you get further into treatment. They also recommend stopping the use of all tobacco products, eating healthy foods to help make your immune system stronger and rinsing your mouth with hot water, baking soda and salt to ensure it’s clean and not a breeding ground for infection.

How to Care for Your Teeth with Cancer

If you experience issues such as dry mouth, mouth sores, jaw pain or sensitive gums, you will want to speak directly with your doctor as they can provide you with more accurate advice and medications. However, to ensure you’re following a great general oral hygiene routine, it’s recommended to brush twice a day with fluoride toothpaste and to floss every day as it helps remove plaque buildup and keep your mouth extra clean. If your mouth and gums are sore, there are alternatives to traditional flossing that might feel more comfortable. If you are still experiencing pain, try soaking your toothbrush in hot water before brushing to make it softer and look for a toothpaste with aloe vera and allantoin as they’ve been shown to help soothe pain in the mouth.

Common Oral Side Effects During Cancer Treatment

During treatment for cancer, your oral health and dental hygiene can be affected, among other things, due to the fact that your immune system is weakened and you are prone to various side effects. Dry mouth and painful sores are some of the most common side effects reported and can cause issues for the health of your teeth as saliva is generally used to wash away food particles and other bacteria. If you find that are experiencing dry mouth, whether in treatment or not, it is best to ask your doctor for artificial saliva and also fluoride gel. This gel will come with a tray that will slip into your mouth and, with the help of the fluoride gel, strengthens and protects your teeth.

Staying Positive About Your Health

Caring for your oral health is just one aspect of working through a cancer diagnosis and subsequent treatment. It is important to consult your doctor with any concerns you might have and gain a solid understanding of what your treatment will require and how it will affect your dental hygiene. Throughout all of it, however, it is most important to remain positive about your health and work to understand that it is a tough process, but with the right care and support, will only make you stronger.

How Can Lung Cancer Patients Stay Involved in Research to Innovate New Treatments?

Living Well With Lung Cancer

Downloadable Program Guide

Noted lung cancer experts, Dr. Lecia Sequist, Marisa Wittebort, a lung cancer advocate with a very rare mutation, ROS1, and lung cancer advocate, Janet Freeman Daily joined this program to provide an expert perspective on the impact of patient involvement in research and how both lung cancer patients and care partners can contribute to bringing new medicines to the market.


Transcript:

Andrew Schorr:
And greetings from Carlsbad, California, near San Diego. I’m Andrew Schorr from Patient Power. Welcome to this Patient Empowerment Network program. I’m so excited. It’s where we can learn how can lung cancer patients stay involved in research and innovate new treatments to benefit the lung cancer community.
Let’s meet our guests. First of all, we wanted to have Marisa Wittebort, who is a ROS1 lung cancer patient, but unfortunately Marisa is having a medical procedure and so she couldn’t be with us. But joining us from New York City is her sister, Jess, who’s been with her every step of the way. Jess, thank you so much for joining us. And, first of all, how is your sister doing?

Jessica Wittebort:
Yes, she’s doing good. Thanks so much, Andrew for having me join today. Marisa’s good. She has another pesky effusion that needs more attention today, so I’m joining you, but thank you very much.

Andrew Schorr:
Okay. Well, all our best to Marisa.

Jessica Wittebort:
Yeah, I appreciate that.

Andrew Schorr:
You know, the role of a care partner such as yourself, a sister, a spouse, and other family members is so critical. Okay.
Let’s also meet someone else who has been living with lung cancer personally and that is our old friend–she’s not old, though–Janet Freeman-Daily who joins us from Seattle. Janet also happens to have the ROS1 mutation like Marisa, and she is so active in going to medical conferences all around the world. Janet, thanks for being with us.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Janet Freeman-Daily:
Thanks for inviting me, Andrew.

Andrew Schorr:
Okay. And, Janet, you–how many conferences have you spoken to that are medical conferences, but you’re a patient who gets up and says, here’s our perspective? How many?

Janet Freeman-Daily:
I think it’s five or six at this point.

Andrew Schorr:
I bet. And we’re going to get–we’re going to talk more about the importance of that. So you’re one side of the coin, as is Marisa, and then we have a leading cancer researcher joining us from Mass General in Boston devoted to people with lung cancer. That’s Lecia Sequist. Dr. Sequist, thanks so much for being with us.

Dr. Sequist:
Thank you for having me. This is really a treat.

Andrew Schorr:
Okay. So you’ve been at medical conferences where you’ve heard people like Janet speak. Does that inspire you when you are actually at what would otherwise be just thousands of cancer specialists, but the patient perspective is put right front and center?

Dr. Sequist:
It’s very inspiring, as I’m sure we’ll talk about. It was especially palpable this year at the World Lung Cancer Conference in Toronto just about five or six weeks ago. Janet was there. There were so many lung cancer advocates there, and this is a conference that’s focused only on lung cancer, and it was really exciting.
But I would say Janet and I have been running into each other at the hallways of medical conferences for many years, and it is always really interesting to get the patient perspective about a big result that was just presented maybe an hour earlier. And I love running into people at meetings and talking to them about it. It really helps inform our research.

Andrew Schorr:
That’s what I was going to ask–go ahead, Janet.

Janet Freeman-Daily:
It’s also very nice to run into a doctor after a presentation and say, what did they just say?

Andrew Schorr:
Right. Right. So do you, Dr. Sequist besides inspiring you, and then there are people in labs who don’t even–you see patients, but there are other people who are only in labs, do you feel that this communication with people who are living it can actually help get information, promote collaboration and accelerate us towards what we hope will be cures?

Dr. Sequist:
Oh, absolutely. It’s a really vital two-way communication road. I think having patient advocates learn more about the research process, both the pros and cons about went research process, and see what all is involved and what hurdles we have to deal with all the time as researchers can be really helpful. We need their help advocating to get rid of some hurdles and the obstacles in our way.
And there is nothing more informative than finding out what really is important to patients, especially when you’re developing a new treatment, hearing from them about what they value, what they–you know, someone who is not living with it may think that a certain side effect is a big deal, yet someone who is taking the medicine will say, you know, actually that’s–I can deal with that if it’s going to help me live longer. And finding out where that balance lies is really important and not something you can just guess if you’re not in the shoes of a patient.

Andrew Schorr:
So, Marisa, you’ve been every step of the way with your–rather, excuse me, Jessica.

Jessica Wittebort:
I’m channeling her, it’s fine. I’m channeling her.

Andrew Schorr:
All right. You’ve been with Marisa every step of the way, and unfortunately she was diagnosed in 2015 at what, age–

Jessica Wittebort:
She just turned 30, yeah.

Andrew Schorr:
She just turned 30. You’re her big sister. From the family perspective what do you hope, with closer collaboration with researchers, practitioners like Dr. Sequist, what do you hope?

Jessica Wittebort:
Well, gosh, I think we’re really just hoping to expedite research, and we want to be part of that journey. You know, I think when Marisa goes in to see her oncologist and he gives her a high five because she’s doing well, you know at a granular level that that relationship and that everybody is pushing for the same thing.
I think a little bit that gets lost in translation sometimes when you can get swallowed by the information that comes out of a conference if you’re not carefully, right, so learning how to translate that information into something tangible and consumable and being able to respond back to your healthcare professionals I think is just that bridge that’s essential to moving things forward.

Andrew Schorr:
And you’ve been to some conferences. I saw you at the Biden Cancer Summit, which had a lot of patients and patient advocates there, but I think you’ve been to–where did you go? To Austria or someplace?

Jessica Wittebort:
Yeah, I went to World Lung in Austria, to meet Janet, frankly. No, I mean, to see some incredible work in progress and some incredible work, and it’s a tremendous amount of content. I probably understood, you know, 5 percent of it, but at least it got me there starting to understand what the language was, starting to understand what the potential impact of clinical trials are, starting to feel just a tremendous amount of hope that lives through science, and to see my colleagues. You know, Janet is pretty much family, so I think these conferences, it’s incredible when patients not only part–you know, really participating, I think that’s a big deal.

Janet Freeman-Daily:
It was also really great for the–there were several ROS1ders there, people who had ROS1 cancer dealing with it at the end of conference, and we got to go up en masse and talk to the researchers about what they were doing, which was educational for us, and I think most of them felt fairly enthused about it too.

Andrew Schorr:
Janet, you’ve spoken at some of these congresses. What do you want to say to that clinical and research audience? What are you trying to bring forward to them as somebody living now, what, four or five years with stage IV lung cancer?

Janet Freeman-Daily:
I was diagnosed seven and a half years ago.

Andrew Schorr:
Seven and a half years ago. So, thanks god, treatment, and you’ve been in a trial for a long time, has just been remarkable for you, life-extending. What’s the message you bring when you speak?

Janet Freeman-Daily:
Well, it depends on the setting that I’m in and what I’ve been asked to speak about. It’s been different topics. Once I’ve talked about value in cancer care and the cost of cancer drugs. Once I’ve talked about the research that the patients with ROS1 were doing. I’ve also talked about the importance of goals of care discussions with the doctors to talk about what our treatment options are and what our chances are of them being effective so we could make our own choices about treatment rather than having the doctor decide what we’re going to do.
There’s a lot of different topics out there that patients can share their background and perspectives on. I think one of my more favorite things is running into Dr. (?) Jean Kooey who created the drug that I’m on and that Marisa started with and that Marisa then took next. She’s the lead chemist on those designs, and we ran into her at the poster session at ASCO and she got to meet the patients that her drug (?) Inaudible, which was a really big deal for her. And we’re all kind of awe struck, fan girl, oh, my god.

Andrew Schorr:
So, Dr. Sequist, does that make a difference? Because there are maybe many thousands of people working around the world on lung cancer now, some people only in labs, and never meet a patient like with a more rare mutation like ROS1. Does that make a difference when that connection can happen?

Dr. Sequist:
Oh, absolutely. I do think it’s really important for people who are working on the basic science aspects of cancer and in a laboratory, a little bit removed from the patients, to meet patients and survivors and see what their work is leading to. At Mass General we routinely have tours of our lab so that the people that work in the lab, not just the lead scientists but even the techs who are there for 10, 12 hours a day working hard for them to see how their work can really make a difference. And I know lots of other centers will do that as well.

Andrew Schorr:
So we’re getting into this age of personalized medicine, and I was in Boston a week or so ago and whether it’s out of MIT or your partners group in Boston, there’s all this computing power coming into play to try to understand what is our personal situation with a cancer and how do you develop or do you have medicines or trials that line up with that. And that’s been a real work of yours, right, is to try to look at the subsets of lung cancer. How are we doing in that? We talk about ROS1 and you have KRAS and ALK and EGFR and all these different types and then some types that haven’t been identified yet, right?

Dr. Sequist:
That’s right. I think if you take the long view and look at 10 or 15 years ago where the field of lung cancer was, it is a totally different landscape today. We have come so far in being able to personalize not only the clinical trials that are available for patients but then subsequently the approved treatments. And there’s been a lot of exciting advances in lung cancer that are a little bit less personalized lately, specifically immune therapy. That works with a bit of a broader brush, but the success in the personalized targeted therapy is unparalleled in other tumors types at the moment, and so I think everyone that works in lung cancer is really proud of how much the field has moved forward.

Andrew Schorr:
But you’re doing detective work, so some of these genes weren’t originally identified, and you have probably a lot more to go, so what’s going on now where for people where a gene wasn’t identified maybe you’ll have that? You’ll find out what the factors are or if somebody switches from one driver gene to another?

Dr. Sequist:
Yeah, there’s a lot of important things that go into that. One is being able to test each patient, and there are now several ways that you can test for the key mutations. The gold standard is still testing tumor biopsy, but liquid biopsies are also coming really into the forefront ready for prime time. Janet and I actually collaborated–well, Janet led the collaboration on an article that we wrote together about liquid biopsies and how it’s–and demystifying some of these things for patient audiences.
But looking at the tumor is important, and then actually important is getting patients to the right trials. You’re not going to be able to prove that something works if you can only find one patient with that mutation. You really have to reach all over the country and sometimes all over the world to find patients specifically for a situation. And that’s one area where patient advocacy groups have been extremely helpful helping bring patients together with the trials that fit their situation.

Andrew Schorr:
So tell me–go ahead. I was just going to–Janet, what’s the message then to people watching so that they can get the care or the testing or help involved to push research further? What do you want to say to people?

Janet Freeman-Daily:
Well, I think one of the valuable things that Lecia brought out is that we are developing or identifying new mutations all the time. When I was first diagnosed nobody knew about ROS1. It hadn’t even been published yet. And when I found out about it and I brought the article to my local doctors in the community setting they didn’t know how to test for it. And yet when I got tested and they found that I had ROS1 I have been on a drug now that I’m coming up to my six-year anniversary for my clinical trial, and I’m still no evidence of disease.
So what I would tell people is it’s really important to keep track of the research and to stay on top of the new developments. And so the patient communities are really good at that because you might find a new option that didn’t exist when you were first diagnosed.

Andrew Schorr:
And so that’s something that you, Jess, and your sister do all the time, right? And so you know you have this ROS1 version of lung cancer for your sister, you don’t know if something will change or other factors will come in, so you keep your ear to the ground very much and connect with the community.

Jessica Wittebort:
Absolutely. So tactically what do we do? We have our Google alerts always set to any medicines that we’ve heard about, any clinical trials that we’ve heard about, any researchers that are working in the space. For us, we have a ROS1 community online which is–we have a public one, and we also have a private one on Facebook where we’re able to just very openly bounce ideas around and talk about things we don’t understand and get those concepts in our heads.
And oftentimes those relationships lead to actually meeting off line. So most cities that Marisa or I visit for whatever reason, whether it’s going to see a doctor or going to an event, we get to meet somebody offline as well. So finding–keeping your ear to the ground, yes. We have great luxury of really–Marisa has a great team, so they will always drive that for her. But I think it’s also something that she is always very keen to share the information that she’s getting so that other people are privileged to have that information as well.

Andrew Schorr:
Go ahead.

Janet Freeman-Daily:
And a few key researchers like Dr. Sequist, Dr. Camidge, Dr. Shaw, at a few key universities are the experts in some of these driver oncogenes, and they’ve been very generous in their time in allowing us to e-mail them questions and say, gee, this question came up in the group, and we don’t have any experience with that. Could you give us an idea of what to do? So the researchers are key to this.

Andrew Schorr:
They are. And, Dr. Sequist, thank you for your devotion. I have a question for you, and that is most people though don’t get treatment at University of Colorado or Mass General or Dana-Farber or City of Hope or MD Anderson, and we could list a bunch of the leading institutions. Most people are told they have lung cancer, they’re at a community oncology practice, they’re terrified, and you’re leading change. You’re on the leading edge, all of you, in lung cancer, but that sometimes hasn’t quite–I don’t want to say trickle down, but you’re on the podium at World Lung or ASCO and you’re talking to a thousand doctors sitting there and we’re hoping that it gets to them, and a patient walks into their clinic, though and maybe some of this isn’t brought to bear.
What can the patient or the family member do so that this knowledge that’s emerging in lung cancer can be brought to bear at the community level? What’s the patient or the family member’s role today?

Dr. Sequist:
I think medicine is changing, and we are no longer in an era where any one doctor can know everything about medicine. I mean, we haven’t been in that era for a long time. And it’s very difficult to be a community oncology, a general oncologist today. There are so many new treatments and new genes and new strategies coming out for every type of cancer in rapid succession, so keeping up with all of lung cancer advancements plus all the other tumor types is quite a challenge.

That’s why I think that now more than ever as cancer gets so complicated it does work really well for patients to be able to connect with other patients and lung cancer specialists online, through activities like this, through many other educational activities that are available and advocacy groups because–just because a community oncologist has never heard of ROS1 I don’t think makes them a bad community oncologist, but hopefully the message is getting out to the community to partner with super sub-sub specialized academic centers if a mutation like this is found in a patient.
Andrew Schorr:
Okay. So, Janet, what do you tell people, what do you want to tell our viewers who were probably treated at least initially at a community center and they have no clue whether they have some subtype, rare or not, of be lung cancer and what to do about it? Janet, (?) Inaudible.

Janet Freeman-Daily:
If a person has lung cancer and it’s non-small cell lung cancer you should have gotten genomic testing at some point, and if you didn’t you need to ask your doctor about that. If your doctor is not familiar with it, and some of the general practitioners and community oncologists may not be as comfortable with it as other lung cancer specialists, then get a second opinion, preferably at a major academic cancer center.
If you want to learn more about this there are a large number of online patient groups where you can ask questions and get educated about this, or you can go to websites of some of the lung cancer advocacy organizations like LUNGevity, Lung Cancer Foundation of America. They have a good deal of information where you can start learning about things to get yourself educated on the topic. It’s–I still hear patients who are stage IV lung cancer, and their doctor sent them home on hospice without ever doing genomic testing. It’s really important that you make sure you get the tests that are in the standard of care.

Andrew Schorr:
So, Dr. Sequist, just back to you. This genomic testing is to see, is there an oncogene or cancer gene that’s driving your cancer that either an approved or maybe a clinical trial experimental medicine may target, right? Okay?

Dr. Sequist:
That’s correct. And, as Janet was saying, it’s vitally important for every patient that’s diagnosed to get tested at a minimum for the genes that correspond to FDA-approved medications, but there are several second-tier mutations that I believe everyone should be tested for because there are clinical trials that even if it’s not available at the community site where they first sought care hopefully it’s available someplace that’s not too terribly far from where they live.

Andrew Schorr:
Okay. So I’m sure that Janet follows this and Jess of course, can the genes change? So, in other words, in lung cancer if Mrs. Jones is seen to have a KRAS mutation, just to pull one out, early on, does that always remain what’s driving her lung cancer, or might it change and there might be a need to test again?

Dr. Sequist:
I think we’re all experts in this, so we can everybody chime in as well. If the cancer truly has a driver oncogene what that means is that every single cancer cell in the tumor carries that genetic mark. Probably the very first cancer cell that came up in the body had it, and then every daughter cell that was created afterwards carries this mark. As patients–so typically these are EGFR, ALK, ROS, MET, RET. These are the ones that we have targets for, BRAF, targeted drugs.
Now, once a patient is on a targeted drug you can think of it like evolution, like survival of the fittest. So a drug is exerting pressure on the cancer, many cells are dying, but sometimes a cell will have a certain characteristic that allows it to live through the drug treatment, and then from there a resistant tumor can grow. And so second mutations or second pathways can become activated after patients have been treated with certain drugs. And the more drugs that people have been exposed to over time the more different subpopulations that might have varying signatures come up.
But you never lose that original mutation. It’s something that is always carried forward. It’s just what else piles on top of it across the different arms. I describe it as different arms of the family or cousins. Like this tumor is a cousin of that tumor because they do have some different characteristics but still that same core characteristic.

Andrew Schorr:
And you were saying about retesting?

Janet Freeman-Daily:
So some drugs we know that if they stop working there’s another drug that you can go to, but as we develop more and more drugs and EGFR, with which Dr. Sequist is very familiar, has more drugs than the rest of us. When patients take certain of those drugs second or third line they actually might develop a different mutation and will have to get retested to find out how to treat that. We’re right on the forefront of learning about how the genomics of cancer works, and we learn new things all the time.

Andrew Schorr:
So, Jess, you and your sister have sought out eminent specialists at major centers, but, as you said, not everybody goes there. What advice do you have to patients and family members, especially family members because sometimes the patient is so terrified just being led through care and the family member has to pick up the mantle? What would you say so that the loved one gets the best care?

Jessica Wittebort:
For us the most profound change has been to find a specialist at an academic institution. I think if you don’t–if you’re not able to do that, it is really important to find your patient group and start asking, what are they doing. What information can you get your head around? And keep your head above water because I really do believe there’s so much hope and there’s so much energy right now and momentum in this space that it’s important to just keep finding, keep looking for the information. And if you’re not getting the answers that you need or are too complicated figure out a way to not feel shy about asking again.

Andrew Schorr:
Amen. So you mentioned earlier, Janet, about getting tested, right?

Janet Freeman-Daily:
Yes.

Andrew Schorr:
So what if the test doesn’t identify anybody? Should they be forlorn? I’m going to ask Dr. Sequist, too. If one of these genes that we rattled off doesn’t show up or driver gene should they say, oh, my god I’m out of luck?

Janet Freeman-Daily:
No, not necessarily. Targeted therapies are easy to take in that you can take a pill once or twice a day, but they’re not the only new therapy that’s come out, and most of the patients who do not have a targeted treatment can take immunotherapy. That’s the new standard of care, and it works really well. I’ll let Dr. Sequist talk to that.

Andrew Schorr:
Let’s understand that, Dr. Sequist. So if somebody doesn’t have any of those genes but both of you have mentioned immunotherapy, how does that work and how does that help?

Dr. Sequist:
So one quick point before we get to immune therapy is that it’s really important if you are told that you don’t have any specific mutations that you make sure that the correct panel was done. Sometimes there are small panels that may miss important genes simply because they’re not part of the panel. So the test may be negative for everything that was assayed, but it may not rule out some of these rare mutations. Like Janet was saying, her mutation wasn’t even known about at that time she had the first testing done so she had to have repeat testing. And this is a very common story. So that’s what I wanted to say about testing.
But immune therapy is–really been a game changer in cancer in general including lung cancer, but this is the idea of trying to get someone’s own immune system so attack the cancer. Our bodies are supposed to do this. Our immune system is supposed to be on surveillance for cancer cells, treat them as foreign and destroy them, but obviously if a tumor grows to a point where you’re getting a diagnosis of cancer something has gone wrong in that process. Usually it is that that tumor is camouflaging itself in some way from the immune surveillance, and some of the new treatments that have been approved over the last couple of years in multiple types of cancer essentially rip off that camouflage, allow the immune system to see that the cancer is there as a foreign invader and start to attack it. In lung cancer this works best on the, as Janet was mentioning, the type of cancers that don’t have a driver mutation, the types of cancers that are more often associated with a history of smoking or exposure to some other carcinogens, and immune therapy has really changed the survival and the treatment options for a large population of lung cancer patients.

Janet Freeman-Daily:
And I just want to reiterate that it’s very important that you get genomic testing before you start immunotherapy because the data we have now indicates that immunotherapy usually does not work for those of us who have driving mutations.

Dr. Sequist:
And it may increase the toxicity of some of the targeted drugs, so not only may it not work but it might harm your chances of having a nice, long response like Janet and Marisa are having.

Andrew Schorr:
Hmm. This is complicated stuff. We talked about how difficult it is for the community oncologist who sees sort of all comers to keep up with this. Let’s just review some of the things that have come up recently at medical meetings that you’ve been at.
So first of all, Janet, from your perspective as a patient, you go to the World Lung meeting, you go to some of the other meetings, what do you think are the big deals for patients? Is it more genes being identified? Is it having immunotherapy work for more people? What are the big take-home messages we should review for people here?

Janet Freeman-Daily:
Well, you touched on two of them. One, there are more genes identified. I’m not sure I’ve got quite the right percentage, but at the moment I believe it’s about 70 percent of patients with non-small cell lung cancer have a driving mutation for which there’s an approved drug or a clinical trial. Is that right, Dr. Sequist? About?

Dr. Sequist:
I don’t know the exact number, but it’s got to be close to there.

Janet Freeman-Daily:
And then there’s immunotherapy, which not only works for some people who didn’t have treatment choices but in some cases continues to work after they stop taking the drug for a good period of time.
But I think one of the other big notes is it appears that immunotherapy may be working for small-cell lung cancer, which has not had a new treatment option in decades, so that is huge.
However, in addition to treatments I would say the next big thing, and it’s not too surprising I’m going to say this because this is what I talked at World Lung, but the fact that we have new patient groups forming around these driving oncogenes, we have enough patients who have been taking these targeted therapies enough, long enough and feeling good enough that they’re becoming active as advocates.
And they want to learn more about their disease, so we now have a group for ROS1 called the ROS1ders, for EGFR, EGFR resisters, for ALK, called ALK Positive, or RET, called the RET Renegades, and a separate group for a subset called Exon 20 group for insertions or Exon 20 of HER2 and EGFR.
And these patients groups are providing guidance to help patients find clinical trials, to help them understand their treatment, to deal with their side effects, to find experts, and we’re also funding research. So there are new research studies being funded by these patients, and the ROS1ders have actually created a study where we are making cancer models of our own rare cancer because researchers didn’t have anything to study, and now they have more cells. In fact, we’ve got, I think, four new cell lines in the past year and more in development.
And we also have three patients who have donated to creating mouse models of ROS1, and they hopefully will be useful for us. And they’ve already had two different publications on the subject. And without it some of the ROS1 research couldn’t be done, so we’re very excited about that.

Andrew Schorr:
Wow, just congratulations to all of you who are involved in this, and I know you’ve got a big smile on your face, Dr. Sequist. We used to have such a very short turn for most people with advanced lung cancer, and now, thank god, with research you’ve done and your peers around the world and in collaboration with patients we have people living much longer, like Marisa, who unfortunately couldn’t be with us today, but Janet and some others who are probably watching.
So that then gives you the opportunity to try to understand them and a lot of aspects of their care and their biology more than you ever could because people are living, right? So that chance for dialogue is really critical to understand how are we not just, yay, we have the medicines helping people live longer but what’s going on, right?

Dr. Sequist:
Yeah. I think that’s right, and it gives us an opportunity to think more critically about how we can do things differently, whereas 10, 15 years ago we were just trying it to find a way to help people live beyond a year. That was the glass ceiling that we were trying to break. And now that we’ve come so far in lung cancer we can really start looking at some of these important questions about sequencing medications, combining medications. What does that do to quality of life? What are other things that affect patients being on clinical trials for years and years, having to go through the scans and the tests? Trying to make clinical trial more accessible to people because of eligibility criteria that are obsolete.
So these are some of the lessons I’ve learned from working with patients in various forums, and it’s really very satisfying for me for sure.

Andrew Schorr:
I know a lot of your work is in EGFR, and if I have it right maybe the incidence of, if that’s the right term, of EGFR, let’s say in the Asian community is higher. Is that right? And so I know the percentage of people in clinical trials is low, like 3 percent. We need more participation of people from different groups so that you can understand how these different mutations are active more or less in different groups, right, and how certain medicines come into play? That’s one of the collaborations we from all groups need to do with you, right?

Dr. Sequist:
Well, I think another–that’s absolutely right, and another really important role that patient advocates can play is to educate their peers about what clinical research involves. Many people in this country are just scared about clinical research. They don’t want to be considered as a lab rat, and they think that’s something maybe for at the very end of the line when you’ve exhausted all other options when in fact some of the most promising clinical trials these days are for the very first treatment that you may take as soon as you’re diagnosed. And having people be aware that clinical trials are not just a way to experiment on a patient but to really offer the patient cutting-edge treatment that they couldn’t get outside of a trial and work together to bring new treatments to approval, that message is critical to get out to the public.

Andrew Schorr:
Right. And can accelerate medicines getting to the goal line quicker, right? I mean, Janet, I know you–a lot of what, for the community living with lung cancer, like you don’t know how long your ROS1 medicine will work.

Janet Freeman-Daily:
That’s right. It won’t last forever. I will eventually have to try something else, and the drug that I take will probably be in a clinical trial. I think it’s important to know that especially for those of us with driving oncogenes but also for people with cancers that don’t have a good effective treatment option, clinical trials may be your best treatment option. Clinical trials provide hope. There’s no guarantee that they will work, but when you don’t have any other option that looks effective or that lasts a long time clinical trials can be very useful.

Andrew Schorr:
So, Jess, a lot of times a physician will say to a patient, well, I might have a clinical trial for you and the patient comes home to review a whole stack of (?) legalist documents to try and simple–and the family member says, oh, no. What would you say to family members too about this idea of clinical trials and supporting your loved one in maybe getting tomorrow’s medicine today?

Jessica Wittebort:
I think it’s really important again to find a group of people that are on a clinical trial so you can see how real it is, how okay it is, you know, sort beat down those major misunderstandings, you know. Fears that you’re going to be given a placebo and then you’re left to go or whatever the case is. I think we’re still getting in a place where (?) ct.gov or Cancer Commons are able to really very clearly articulate it. The research is there, the information is there, but I do find it still a bit daunting for people who probably are just freshly diagnosed to understand what it means, so I think–

Andrew Schorr:
Right. As Janet said, there are people who can help you with the lung cancer groups she’s rattled by, online groups. There are all sorts of people who can help you, so I want you to–I hope our viewers will take advantage of that.
So, Dr. Sequist, people–Jess just mentioned about people have this fear of getting a placebo. If you’re in a trial, people want to get the good stuff even though you’re not sure what the good stuff is or how good the good stuff could be, but are they taken care of no matter what?

Dr. Sequist:
Patients are absolutely taken care of no matter what. There are many different kinds of clinical trials. Some of them have one arm where everyone on the trial gets the same treatment. Some of them may have multiple arms, and there could be a randomization where a computer basically rolls the dice and tells you and your doctor which arm you’re going to be placed in and you don’t have a choice. But patients are informed about the design of the trial and the various treatments before they sign up. We’re still–scientifically, before something can become standard of care, we still need to compare it to the old standard of care. Luckily, in lung cancer there really aren’t too many spaces left where standard of care would be placebo, so most patients getting lung cancer clinical trials are treated with a standard chemotherapy or a standard targeted therapy or a standard immune therapy, and then the experimental arm might be a variation on that or something totally different.
But it’s really important, and if you do participate in a clinical trial the person who is talking to you about the participation and getting your consent will inform you of all those things. What are the options? What could you be treated with? What is the purpose of the trial? How will it help you as a participant? These are all really important things to understand before you jump in.

Andrew Schorr:
Here’s a question–oh, sorry. Please.

Jessica Wittebort:
I was just going to say that Marisa just signed a stack of papers in Boston this week for participating in the blood biopsy trial, and that’s maybe the fourth pile of paperwork I’ve seen her sign. And it was an incredible process of just her being able to ask any questions, the nurse practitioner sitting down with her answering, answering everything and anything and understanding what it meant. And, you know, it’s–I just think we probably need to figure out how to eliminate some of the fear and the mystery around that process.

Andrew Schorr:
We did a program the other day and the replay will be posted soon with Dr. Richard Schilsky who is the chief medical officer of ASCO, the big cancer organization, and they’re really working hard with industry and government to simplify the forms. And, for instance, for people where English is not their first language to make sure that things are explained to you in your language, whether you read or if there’s a translator there so that you fully understand.
Here’s a question we got in from Ed, Dr. Sequist. He says, I’ve been an active participant in a Phase 1 trial for nearly three years. What is the average length of time it takes for a clinical trial to get to FDA approval?

Dr. Sequist:
That can really vary. I don’t think there is a standard answer, but a lot of people ask me, okay, doc, I’m going on to this Phase 1 trial at what paint will I be graduated up to Phase 2 or Phase 3? And, you know, patients usually don’t switch from a Phase 1 trial to a Phase 2 or 3. The drug development may continue and–continue on its pathway towards FDA development, but patients usually stay in the same trial that they started on.
The record time in oncology for first patient dosed–interval between first patient dosed in a Phase 1 trial to FDA approval was probably for crizotinib, which is an ALK, ROS and MET inhibitor, where the time was, what, about three years, Janet?

Janet Freeman-Daily:
Inaudible.

Dr. Sequist:
But most drugs take a little longer than that. But when I was training the–what I was taught was that it usually takes 10 years for a drug to get from Phase 1 to approval. Thankfully, that is not the case anymore. Most drugs are getting there in three, four, five years.

Andrew Schorr:
Well, I think, as Dr. Schilsky said the other day, they’re really trying to work with the FDA, the NCI, industry to try to do it, but part of it–now, for instance, the government is looking for patient-reported outcomes. How do things affect the patient in their life? So again doesn’t that come into play, too, Janet, that we need to be–we need to be not just part of the trial but we need to be giving information to help with as decisions are made about whether a new drug is a big deal, right?

Janet Freeman-Daily:
Yeah. Patient-reported outcomes are just starting to be incorporated into clinical trials, and it will be great to have them more involved and for patients to be able to provide inputs that are important to them about how they feel on the drug and how it affects them so that we will have more information about side effects when a drug gets approved. But it’s still fairly early.
But I want to go back to one thing that Dr. Sequist said, that the FDA is trying to put programs in place that will help get drugs approved faster. So the clinical trial that I’m on has been going for seven years and will keep going even though the drug is already approved because the drug was approved under what they call accelerated approval based on a Phase 1, 2 trial. Usually the FDA used to require that you had to have a big Phase 3 trial with hundreds of people where you compare the drug against the current standard of care and get a positive result before you could get the drug approved.
But now they’re making drugs for small populations like ROS1 patients. We’re 1 percent of the non-small cell lung cancer population, and you’ll never get enough of us together in one place to do a Phase 3 trial. So the FDA has something in place that allows you to approve drugs based on the Phase 2 trial. Everybody in this Phase 2 trial knows they are taking crizotinib. There is no placebo. So there are–the clinical trials are evolving.

Andrew Schorr:
So, Dr. Sequist, let’s back up for a second. So we’ve had–we have these meetings that you all go to, World Lung meeting, which was in Toronto I think a few months ago. And you have the ASCO meeting and others you probably go to around the world. What do you think is a big deal now? And I know I’ve seen you on the podium at some of these meetings. What do you think is a big deal for patients if you take away from some of the key studies that have been–you’re releasing data on?

Dr. Sequist:
It’s been a huge year for lung cancer. I mean, the standard of care has changed in lung cancer in almost every little corner that you look in. A year ago or certainly two years ago most patients who were diagnosed would get chemotherapy as the first pass treatment. If you happened to have one of the driver mutations then you would try and get one of those treatments first.
Now the standard of care has completely changed. Most patients get immune therapy with or without chemotherapy. There are new approved drugs for ALK and for EGFR in the frontline setting. There’s a new standard of care for stage III lung cancer which we haven’t had in 30 years. There’s a new standard of care for small-cell lung cancer which we haven’t had in 30 years. There’s more evidence from this past year about screening for lung cancer with low-dose CT scans and how this is really effective at diagnosing people earlier and saving lives, potentially especially so in women, we learned at World Lung. So every corner of lung cancer that you can shine a light into there’s been advancements over the last one to two years. It’s really quite amazing.

Janet Freeman-Daily:
We’ve also had one liquid biopsy approved where they can use a blood test to determine whether you’re eligible to take a certain kind of drug. That just happened last year I think.

Andrew Schorr:
So, Jess, you listen to this as a family member. What hope do you take away from that for your sister? Jess, could you hear me okay?

Jessica Wittebort:
Yes, sorry. You’re breaking up a little bit, Andrew.

Andrew Schorr:
I said you hear what Janet and Dr. Sequist were just saying. What hope can you take away from this because you worry about your sister of the week?

Jessica Wittebort:
Every single day I worry about her. And she has to worry about me as well. I often wonder who the real carer is. But, frankly, it’s, you know, she was given a brutal diagnosis three years ago, and she’s kicking. You know what I mean? She’s kicking. She’s doing great. She’s doing yoga teacher training. You know, she has good days and bad days, and I just think there’s an incredible amount of hope.
So get your head in the game, get some information. Get yourself a plan, and you move forward. And if you don’t find the doctor, and it happens all the time, can’t find the doctor you can trust or you can get the right answers from, then you keep looking.

Andrew Schorr:
So here’s some questions that we’ve got in. And, again, if our viewers have a question just send it to questions@patientpower.info.

Kevin writes in for you, Dr. Sequist, for many cancer patients there’s a learning curve. What are your thoughts on how a patient might know when they’re ready to learn and what are the first-stop resources that might give them education they’re ready for? And, Janet, I’m sure you’re going to weigh in. How about the ready to learn? Because otherwise at the beginning you’re drinking–you’re terrified, and you’re drinking from a fire hose?

Dr. Sequist:
Yeah, that’s a great question and I don’t think it’s one-size-fits-all. I mean, patients, it’s like all of us. They come with much different preferences about how they like to learn, about what they want to know, about whether they want to be the primary person learning things or they’re going to designate a family member to help them with this information.
Some people like to learn on the internet. That can be tricky because there’s a lot of bad information on the internet in addition to a lot of good information on the internet. Some people aren’t that into the internet, and they need to learn in-person or through meeting people or phone calls. Luckily, the lung cancer community has so many support systems and education systems that are out there.

Janet mentioned a few, LUNGevity and the American Cancer Society has some information on their website, but a lot of academic medical centers also have information on their websites about lung cancer and resources to connect you to learning more when you’re ready.

Janet Freeman-Daily:
So just to add to that, because there are a lot of wonderful, very educational resources on the internet the Lung Cancer Social Media group put together a reference page for vetted online resources. So if you go to lcsmchat.org under resources and look for what’s there you can find a list that includes links under various categories like for those who are newly diagnosed or looking at lung cancer screening or whatever. And on that list we’ve tried to pull a sample from all of the various pages we know of, all the various organizations that have good lung cancer information. So you can start there.

Andrew Schorr:
Dr. Sequist, I wanted to call out small-cell lung cancer, which I know is the minority of lung cancer. And Janet referred to immunotherapy there, and you talk about overall about hope. Where are we with small-cell now?

Dr. Sequist:
Well, there was a very exciting presentation in Toronto at the World Lung meeting and it got published in the premier journal, The New England Journal of Medicine, that same day that set a new standard for small-cell lung cancer, something that–it was actually really moving. The whole audience burst into applause and cheered essentially when this result came up because for most of us in the audience we had never witnessed an advance in small-cell lung cancer in the course of our career. So this advance is taking the standard chemotherapy for small-cell and adding immunotherapy to it, and patients had an improved survival when that happened.

Andrew Schorr:
Okay. So where do we go from here? Janet, you’re living with it. You wonder how long your medicine is going to work. You have one rare subtype. Other subtypes are being identified and then other people

where it hasn’t been identified yet. What do you want to say to people as far as just keeping on keeping on, if you will, and the importance of a dialogue with a doctor, a researcher in partnership?

Janet Freeman-Daily:
I think the only thing I would make sure everyone does, no matter whether you want to know all the details, whether you want to be involved in research is that it’s essential that you tell the doctor what is important to you. They can do all the rest of it if you need them to, but they can’t know whether it’s more important to you to try every last treatment no matter how lousy you feel, or whether you would rather make sure that if you can’t get out and walk in the woods then life isn’t worth living. They won’t know if you don’t tell them, so it’s important for you as a patient to start thinking about what matters to you in terms of your treatment.
Likely, you’ll be on more than one treatment at some point if you have metastatic lung cancer, and you need to know whether the side effects are acceptable to you. So even if you don’t want to do the research at least be able to tell the doctor what matters to you. I hope Dr. Sequist that you get some patients who do that.

Andrew Schorr:
So, Jess, so some people have trouble speaking up for themselves. I don’t think you’re sister is that way, but you go with her to a lot of treatments and visits. What would you say to family members to support their loved one, and if their loved one isn’t, isn’t feeling strong enough to speak up that the family member has permission to do that and that it makes a difference.

Jessica Wittebort:
Yeah, I think Marisa has her boyfriend, my dad, (?) Inaudible happy to hem and holler about the questions we have and the questions that she raised since the last time we saw the oncologist. But more recently she referred to us as the peanut gallery. I think she’s, you know, at the beginning of this diagnosis I was the one that reached out to the ROS1 group, and now she has a pleural effusion and she’s trying to figure out all the places that that pleural fluid should go to support research.
So I think that the journey will change. I hate that word, journey. I think the path changes as you go. You know that old when you come to a fork in the road, you can take the path or whatever it is, and I think you just have to figure out how to be flexible and flex with that journey. There was–one of the really nice pieces at the Biden Cancer Initiative, I’m terrible with names, the athlete was talking about, you know, everybody talks about diagnosis and the shoot for the cure, but it’s that middle, it’s that middle part that is so tenuous and you have to get really comfortable with the uncomfortable middle part.
So I think, gosh, it could be a strain and stress on your loved ones, and I think the communication is just one must of the exercise as you go, and if you can figure out how to lean into that as a carer, as a patient, as a loved one, then you’re probably ahead of the curve.

Andrew Schorr:
Thank you for that, and we wish your sister all the best, Marisa. My last question is for Janet and then Dr. Sequist. So it used to be the doctor was in the white coat, and the doctor said we’re going to do this, and you were scared, and you went down the hall to have a scan or this or a biopsy, whatever, you just did it. You’re just sort of literally the walking wounded, and you and your family were terrified. And whether you understood or not you sort of nodded your head, and that’s what would happen.

Dr. Sequist, do you welcome the change? Do you welcome the change that we’re sort of all in this

together? And I don’t mean just physicians but I mean researchers too, that this feeling that the patients, the family members, that together, we can solve things. Alone, it’s slower or more difficult?

Dr. Sequist:
Oh, yeah. It’s a very welcome change. I’ve gotten a lot of information and education as well as satisfaction from participating in the lung cancer social media group that Janet mentioned. It’s really great to be able to connect with people on Twitter who are researching lung cancer around the world or who are patients living with lung cancer around the world. And it’s a way to get lightning-fast updates about conferences, and everybody working together towards a common goal is a good feeling to be in that pack.

And I would say to patients out there if you’re in a relationship with a provider where it feels more like what you were describing, Andrew, like that you’re just being told what to do and you’re not being listened to or you don’t have the ability to speak up or have your loved one speak up for you, you need to seek out a different oncologist. Because it’s too important.
It’s too important of a disease to be dealing with someone you don’t have a great relationship with. And I would define a great cancer patient/oncologist relationship is one where both people can feel free for express what’s on their mind and to listen to each other and just feel heard and feel part of the decision-making.

Andrew Schorr:
I just think has a tragedy if, as you say, the landscape is changing so much–we have a long way to go, but it is changing so much in welcome. What a shame if you or your loved one passes away because there wasn’t a certain test done or a wide enough panel testing and there was something either approved or in trials that could make a difference to extend life. What a tragedy.
So Janet, I’m going to leave the last sort of empowerment message to you, what you want to say to people so that that doesn’t happen.

Janet Freeman-Daily:
I think there’s been a lot of good comments in the entire presentation along those lines. I think there’s a lot of evidence to show that engaged patients with serious diseases live longer. That patients who become more educated about their disease when it’s on the cutting edge as lung cancer is right now, they have a much better chance of making sure that they’re getting the best care.
But I also want to point out one interesting thing that’s evolving as we get these more empowered patient groups. We actually had a doctor, a researcher approach us because he had heard that ROS1 patients supposedly didn’t have as many brain mets as outpatients did, and that didn’t seem right to him. So we actually worked with him and did a survey on our own patient group and were able to tell him, yeah, it’s a lot more common than people are giving it credit for, which stimulated a whole new path of research that’s changing the way that people think about the disease. And if we had not had that open communication between the patients and the researchers, if we hadn’t had the empowered patient groups that survey wouldn’t have happened. So I think this change in paradigm being patients learning about their disease and getting involved in patient groups is making a huge difference.

Andrew Schorr:
Well, Janet Freeman-Daily thank you for being with us once again. I hope we get to do this for years and years, Janet, and one day we can say cured. Wouldn’t that be great? And I’m so delighted to see you and for joining us.

And Jess Wittebort, thanks so much for being with us too. All the best to your sister Marisa with the procedures she has, and, as you say, she’s kicking it, and I hope that keeps happening.

And Dr. Lecia Sequist from Mass General, thank you for your devotion to patients and helping lead the way in research so that we can really everybody can get the personalized care they need.
I’m Andrew Schorr from Patient Power. Remember, knowledge can be the best medicine of all.


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