AML Treatment Options: What’s Available?

AML Treatment Options: What’s Available? from Patient Empowerment Network on Vimeo.

Dr. Jessica Altman reviews currently available treatments for acute myeloid leukemia (AML), including chemotherapy, stem cell transplant, and clinical trials.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about Dr. Altman here.

See More From The Fact or Fiction? AML Series


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Fact or Fiction? AML Treatment and Side Effects Resource Guide

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Can AML Be Cured?


Transcript:

Patricia:                         

Dr. Altman, let’s talk a little bit right now about treatments that are currently available for AML. What kinds of things might patients want to familiarize themselves with?

Dr. Jessica Altman:    

So, we are at a point in AML therapy where there’s not just one choice of treatment.

There are a number of choices that depend on patient characteristics, disease characteristics, and patient goals. So, there’s a lot that the physician with their patient and family members take into account and consider when they’re coming up with a therapeutic strategy.

Patricia:          

So, give us a couple of examples. Chemotherapy is one way to treat AML, correct?

Dr. Jessica Altman:    

Correct. So, the treatments all stem from a chemotherapy backbone. And there are more intensive chemotherapy regimens that usually involve a long, in-patient hospitalization and less intensive chemotherapy regimens. Those chemotherapy regimens can sometimes be combined with targeted therapy based on the genomic structure or the mutations present in leukemia cells. 

Patricia:          

Stem cell transplant is also an option as well?

Dr. Jessica Altman:                

Stem cell transplant is an option that is utilized ideally after the leukemia is in remission as a way of maintaining disease control.

And for some patients, that is the best approach for a curative option, and some patients’ leukemia does not require a stem cell transplant.

Patricia:          

Clinical trials available as well for AML, doctor?

Dr. Jessica Altman:    

So, we feel very strongly that the best treatment strategy for most patients is a well-designed, appropriate clinical trial for all phases of AML therapy. It’s because of research and clinical trials over the last number of years that we have had advances and more approvals for the treatments of Acute Myeloid Leukemia.

How is an AML Treatment Approach Determined?

How is an AML Treatment Approach Determined? from Patient Empowerment Network on Vimeo.

 AML expert, Dr. Jessica Altman, discusses the factors she considers when making treatment decisions for patients.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

See More From The Fact or Fiction? AML Series


Related Resources

Why Should Patients Be Hopeful About AML Treatment Options?

Office Visit Planner

Can AML Be Cured?


Transcript:

Patricia:     

So, when you’re talking with your patients, what kind of things are you considering when determining how to best treat AML?

Dr. Jessica Altman:    

So, that’s a great question. This is something that is the basis for the entire conversation that I have with my patients and their family members. 

I consider patient goals and patient fitness, other medical conditions, and a lot about the biology of the leukemia. If someone has an acute leukemia that is expected to be highly sensitive to intensive chemotherapy, then that is something that we want to think about. Versus if the patient has a disease that is not expected to be as sensitive to intensive chemotherapy, we frequently like to consider other alternatives in that space.

Patricia:     

So, in terms of options, as a patient what kind of things should I be thinking about when I’m working with you as my doctor about what the best treatment for me might be going forward?

Dr. Jessica Altman:    

So, I think the goal of the initial meetings and the initial consultation between a patient and their healthcare provider is to explore those things. We take a detailed history, understanding patients’ other medical issues. In addition to that, the social history and patients’ goals are very important, as things are not always a yes or no.  

They’re not dichotomous choices. And to be able to understand a patient’s goals, and for the healthcare provider to be able to explain what the intent of treatment is helps both parties come to the right decision for that individual patient.

Clinical Trial Toolkit

Why Should Patients Be Hopeful About AML Treatment Options?

Why Should Patients Be Hopeful About AML Treatment Options? from Patient Empowerment Network on Vimeo.

Registered nurse Mayra Lee explains why AML patients should be optimistic, emphasizing the positive impact of recent treatment approvals and personalized medicine.

Mayra Lee, RN, is an outpatient clinic nurse at Moffitt Cancer Center. More about the expert here.

See More From the The Pro-Active AML Patient Toolkit


Transcript:

Mayra Lee:

Other advice that I have for AML patients or reasons to be optimistic is a lot has happened in the last three years in AML that hasn’t happened in 30 years. There has been a lot of drugs that just recently got approved. There has been a lot of research. Cancer itself is moving in leaps and bounds and it’s incredible what’s happening actually in our centers and the academic centers with research and clinical research and personalized medicine based on the cytogenetics of the diseases.

There’s so much of that going on and there is so much focus on that that there is a lot of hope. Recently, in the last two years or so, there have been at least five or six medications approved for AML that didn’t exist before in the market. So, it gives hope to other patients that didn’t have hope before. And clinical trials give hope to those patients as well. We can’t promise you any results on a clinical trial but there’s certainly a medication or a treatment that wasn’t available to you beforehand or that wasn’t available if it’s not outside of the setting of a clinical trial. So, keep optimistic. Keep thinking that you’re going to beat this because if you come into this arena of AML feeling defeated that is going to reflect, actually, on everything.

Patients that have a great attitude, have a positive attitude, think that I’m here, we’re going to do this together do the best.

A Conversation With Becky Pleat

Specialty Pharmacy and the Patient Journey with Specialty Medication

In this segment of A Conversation With, Becky Pleat the Associate Director of Medical Managed Care Oncology Specialist at Sanofi discusses specialty pharmacy and the patient journey. Becky answers the following questions:

  1. What is a specialty drug?
  2. What is a specialty pharmacy?
  3. Where can patients find a specialty pharmacy?
  4. How do patients receive a specialty medication?
  5. Will a specialty medication be covered by a patient’s health plan?
  6. What kinds of services and/or resources are offered at specialty pharmacies?

What Are the Current Treatment Options for AML?

An expert panel help viewers understand more about the evolving field of AML treatment. This includes identifying prognostic factors and determining patient subtypes to setting treatment goals and selecting a suitable course of treatment. The panel was made up Dr. Uma Borate of Oregon Health & Science University, Amanda Fowler of The Leukemia & Lymphoma Society, and patient advocate, Don Armstrong

Downloadable Program Guide


Transcript:

 

Andrew Schorr:

And greetings from Los Angeles.  I’m Andrew Schorr.  Welcome to this Patient Empowerment Network program produced in association with the Leukemia & Lymphoma Society and with support from the following companies:  Celgene, Daiichi Sankyo, Jazz Pharmaceuticals and Novartis.  We thank them for their support, but be advised no outside party has any editorial control. 

In this program we’re going to discuss the latest the treatments for acute myeloid leukemia.  We have a wonderful panel, and over the next hour we will be discussing the options, but of course always discuss this with a healthcare team that you trust so you get the care that’s right for you or a loved one.  Also, if you have a question send it in to aml@patientpower.info, aml@patientpower.info, and we’ll get to questions as we can. 

Today with us with have with us a pretty long‑term survivor of AML joining us, and we also have an information specialist from the Leukemia & Lymphoma Society and a noted physician researcher from Oregon Health & Science University.  So let’s go around the country and meet them.  I’m in Los Angeles. 

Let’s go to Fort Worth, Texas, and joining us now is Don Armstrong, who was treated for AML.  Gee, Don, in 2005 your whole world turned upside down, right? 

 

Don Armstrong:

It absolutely did.  September of 2005 I had no idea there was anything wrong with me until I had a couple ladies tell me on a Friday afternoon I looked horrible.  That ultimately led me to see my general practitioner, and a couple of days later I was diagnosed with acute myeloid leukemia, and from there right into the hospital, right into treatment. 

 

Andrew Schorr:

Right.  And you were in the hospital for a long time. 

 

Don Armstrong:

I was.  I was in the hospital the first time for 33 days. 

 

Andrew Schorr:

Wow.  And ultimately you had a transplant, which is one of the approaches still for AML, and you survived. 

 

Don Armstrong:

I did.  I did.  Yeah, it was interesting.  That first couple of days in the hospital there was so much activity going on around we and I couldn’t understand why I was getting so much attention until one of the nurses kind of pulled me aside and said, you understand you’ve got a 25 to 30 percent chance of surviving this type of leukemia, don’t you?  And I said, now I do, yes.  So it was quite a shock to the system, and it was something that‑‑you just have to kind of hang on and just go with the program as much as you can. 

 

Andrew Schorr:

And a shock to the family.  I mean, it’s a family affair. 

 

Don Armstrong:

No question about it.  Whenever you’re diagnosed with cancer, no matter what the cancer is, it’s just not you.  The entire family is involved.  And I had a great support system.  My dad and my brother and my sister came from different parts of the country just to be with me and support me.  I had an unbelievable group of family and friends that were there with me every single day. 

 

Andrew Schorr:

And you had a transplant.  Where did the donor cells comes from that sort of rebooted your immune system? 

 

Don Armstrong:

That’s a great question.  I’m actually currently still looking for my donor.  My donor, he was happy.  I know he’s a male.  He was excited that he was able to help me, but I have never able to connect with him.  I’m trying again.  I just‑‑so through the Be the Match I got my stem cells, and fortunately there was someone there that was willing to give my life a second chance. 

 

Andrew Schorr:

Now, Don is very active with the Leukemia & Lymphoma Society, which is a partner in this program.  Don, you’ve spent many years now, your career has been in golf and you were a golf superintendent, and yes, you sprayed pesticides on the golf course.  You’re devoted to giving back.  Talk the a little bit about that and what you try to tell patients and families so they can get through this hopefully successfully, as you have. 

 

Don Armstrong:

You know, like we had talked about, I had no idea there was anything wrong with me when I found out I had leukemia, and I was in for a pretty big fight of my life.  After five rounds of chemo and a stem cell transplant, making it through that, I felt like I had been given a second chance, so I wanted to find a way to give back.  And I found the Leukemia & Lymphoma Society.  I found one of their campaigns, Team in Training.  Started doing the endurance events and raising money for that organization.  Just did my 2015 retraining event, but through it all I really wasn’t doing it just to run a marathon.  I was doing it to raise money for research so that somebody else hopefully didn’t have to go through what I went through.  So for me that was a big shift in my mindset.  That eventually led me into being a part of the board of trustees, and I continued along that line.  And I try to stay up on as much about AML as I can, and I talk to as many patients around the country as I can whenever I’m given the opportunity. 

 

Andrew Schorr:

Well, you’re going to hear a lot today, and research has paid off.  Let’s go up to Colorado outside Denver where Amanda Fowler is an information specialist with the Leukemia & Lymphoma Society.  And that means if you call, and I urge you to, whether a patient or a family member, they can help because based on research the world of AML has changed significantly and gives people a great deal more help and is changing those statistics that Don talked about.  Amanda, welcome to the program. 

 

Amanda Fowler:

Thank you it so much for having me. 

 

Andrew Schorr:

So I’m right.  Research has been paying off just in the last year or two and even with more research coming our way, right? 

 

Amanda Fowler:

It’s incredible.  There have been drug approvals in the last two years.  There are numerous clinical trials.  We are really seeing AML treatment change for the better at a pretty rapid pace right now. 

 

Andrew Schorr:

Okay.  So just to be clear, if someone who is watching now calls the Leukemia Society like the national number, and maybe you can tell us again, how do they get to you so you can help them sort this out? 

 

Amanda Fowler:

Absolutely.  It’s really easy to reach an information specialist.  We are open 9 a.m. to 9 p.m. eastern time and our number, which we can repeat at any time, is 1‑800‑955‑4572, and that will take you straight to an information specialist.  And once you reach us we’re really there to talk and figure out exactly what you need. 

So if you’re not sure if you need help or not, give us a call anyway, and we can go over a lot of the resources and services from psychosocial support to financial resources, disease education.  We have a clinical trial support center, so a whole variety of resources, and we encourage people when in doubt to reach out to us. 

 

Andrew Schorr:

Okay.  All right.  Let’s hear about the research.  So joining us from Portland, Oregon, at Oregon Health & Science University is Dr. Uma Borate, who is a hematologist‑oncologist.  Dr. Borate, thanks for being with us. 

 

Dr. Borate:

Absolutely.  Thank you for having me. 

 

Andrew Schorr:

Okay.  So we’ve alluded to changes in AML, payoffs in research.  You’re still in the lab moving research forward with your peers around the world.  You all are making progress, am I right?  The world and the options, the combinations, things you’re researching, that’s all changing incredibly fast. 

 

Dr. Borate:

It absolutely is.  And I just wanted to first just appreciate Don and his journey because we see patients like him every day, and we deliver these very shocking and stressful diagnoses to patients and kind of see the journey of absorbing what this means for them.  The family rallying around them.  And then the treatment and the eventual, you know, the role that takes them hopefully to a cure.  And I just‑‑every day when I talk to my patients I just applaud their courage.  So, Don, I just wanted to put that out there.  You guys are awesome. 

With that said, I think in the last I would say four to five years, and Amanda can attest to this, we’ve had over nine FDA‑approved therapies for AML after about four decades of no progress.  And a lot of this has come with discoveries in the lab where we have identified specific genes that have had genetic changes, what we call genetic mutations, that lead to a patient developing AML. 

And now we have what we call targeted therapies where we can target that specific genetic mutation and therefor destroy the AML cells in a way that doesn’t expose the patient to a lot of additional toxicities.  However, for a certain subset of the AML patients, like Don, we know that these targeted therapies can work for a while, but if you are going for what we call a curative active therapy, for a lot of patients transplant is still right now one of the most, I think, advocated and proven curative therapies out there. 

 

Andrew Schorr:

Okay.  So let’s talk about testing.  So somebody is diagnosed with AML.  What should happen now so that you as a specialist, the doctor, the team that they see, they know what version of AML you have and whether it matches up with either one of these approved therapies or maybe something you at an academic medical center are researching that could be the drug of tomorrow? 

 

Dr. Borate:

So I think that’s a great question, and for patients or family members or anybody else listening out there I think what you a alluded to as the most crucial step in the diagnosis of AML and the subtype of AML is the testing.  So as soon as we identify a patient, like Don described, typically it’s, you know, you don’t feel well.  You go to somebody, they say, oh, my god, your blood work doesn’t look right.  You go to another doctor. 

The first thing that we ask that happens is when a bone marrow biopsy, which is the diagnostic procedure that gives you the diagnosis of AML is done, that it be subjected to adequate genetic testing.  And by this I mean there are many, many laboratories out there that do what we call expanded genetic mutational panels, and they test for all the different genes that could have a mutation that potentially could be targeted or make the patient a candidate for a clinical trial in the future. 

Leukemia & Lymphoma Society is sponsoring an extremely revolutionary trial called BDML, which we are a part of, which does this testing and returns the results back to the clinical provider or the physician in seven days, which is really unheard of in terms of a timeline.  This used to take about two weeks on average. 

And so in seven days I know all the genetic changes in my patient’s leukemia and I can determine, hey, is this the right therapy for them?  Should they go on a clinical trial that we have?  And BDML offers several of what we call (?) Inaudible that are used to match them to the appropriate clinical trial or the appropriate drug.

 

Andrew Schorr:

Okay.  So, Amanda, let’s talk about this for a second.  So, oh, my god, a patient is diagnosed with this acute condition.  Don found himself in the hospital right away, and I understand there can be different versions of AML.  Some like do not pass go, boom, you’re going to the emergency room at the hospital right away, or some there’s a little more time.  But a call comes to you, and people want to feel confident that where they are or where‑‑do they go to this hospital or that hospital, this clinic or that one.  They get someone who is knowledgeable when the whole world of AML has been changing. 

So how do you counsel people so they get the right testing and just all the range of options are considered for them? 

 

Amanda Fowler:

Sure.  Absolutely.  So I should say a lot of the calls, particularly for the acute leukemias, actually come not from the patient but from the caregiver.  The patient is often sick and overwhelmed, and it’s a family member who is making the calls.  Of course we are having to talk to both the patient or the caregiver, but it is really important to be at a center of excellence for this diagnosis. 

Not all hospitals are equipped to handle AML.  If you’re lucky, a local hospital will see that and send you on to the bigger center, but sometimes that work does fall on the family member.  We recommend that people go to university‑type settings or National Cancer Institute comprehensive cancer centers.  These are going to be the larger hospitals that understand what tests are involved.  They will have clinical trials as options, and they will be knowledgeable on the latest treatment options. 

 

Andrew Schorr:

Right.  So, Don, just to you.  You talk to patients, and you speak around the country.  It takes a lot of courage for a patient or family member to say, thank you, Doctor, but I think we’re going to go, take mom or dad, we’re going to go over there because, you know, I mean, hospitals are competitive, right? 

 

Don Armstrong:

Absolutely. 

 

Andrew Schorr:

But you and the family want to make sure that your loved one gets state‑of‑the‑art care.  What would you say to them to be a good consumer? 

 

Don Armstrong:

Well, I agree with what Amanda said.  I think it’s important that you’re in the right hospital, the right setting because not all the hospitals can actually handle the diagnosis of AML.  So I think it’s really important that you’re in a center that can treat that, that’s got experience treating it.  And so I always tell patients call the Leukemia & Lymphoma Society’s IRC and find out where is the best place to go. 

 

Andrew Schorr:

And here’s Amanda.  And, Amanda, you have a medical advisory board.  You keep lists of AML specialists, right?  So you can actually say where in where you live, in Kansas, in California, in Texas, etc., here are centers of excellence, right? 

 

Amanda Fowler:

Yes, absolutely.  We will talk to patients about where to go, wherever it is that they live.  And then occasionally if it’s later on in the treatment and they’re considering transplant they may even look to travel, and we’ll help discuss any option that they want to get them to the center of excellence. 

 

Andrew Schorr:

Okay.  All right.  Dr. Borate, let’s go back to the basics just for a second because we have people who are trying to understand what went wrong.  I’m a leukemia patients too, but with chronic lymphocytic leukemia, but I know that our bone marrow often in our hips and bones is the blood factory.  What went wrong in that blood factory, and how does it show up in AML? 

 

Dr. Borate:

So, thank you, Andrew.  I think that’s the so‑called million dollar questions is we know that there’s a combination of factors that can cause what we call these genetic mutations that then go on to lead to the actual disease. 

So whether it be CLL, which you alluded to, or AML, age is a big factor.  So as all of us grow older the unfortunate reality is as our cells divide they accumulate genetic changes that (?) Inaudible repair, so that’s one thing that happens to all of us.  Environmental and genetic factors play a big role, and I think the new emerging field in this is what patients would ask us, why did I get this?  We would say, well, you were unlucky.  You had this mutation.  Something happened. 

But now we know about 10 to 15 percent of leukemias actually have a genetic or what we call an inherited component.  So if you talk to patients they would have‑‑some patients have a very strong family history, not just of leukemias or lymphomas, which are blood cancers, but other cancers.  And I think it’s really important to nail that down and explore the inherited aspects because for patients like you or Don, if you have kids and grandchildren, you know, those have far‑reaching implications down the road. 

However, 85 percent of these leukemias are what we call sporadic, meaning they just came about because of environmental and genetic factors that sort of played a role in one or two cells developing the mutation and then there is a competitive advantage for these cells.  They start growing, you know, without any checks and balances, and once that happens they start crowding out the healthy cells in your marrow and they sort of replace, as you said, the nice, healthy cells in your bone marrow that should be making your red blood cells, white blood cells and platelets. 

And sometimes the analogy that’s given is you see these weeks on a lawn and once the weeds start growing they kind of take over all the healthy grass because they compete for nutrients and water, and then all you get is a lawn full of weeds. 

 

Andrew Schorr:

Okay.  So somebody comes to the emergency room, like Don looked sick.  Is it fatigue?  Is it bleeding?  Is it just what‑‑how do people present, as you doctors say? 

 

Dr. Borate:

So typically patients present with this feeling that they’re not‑‑they just don’t feel well.  Typically it’s fatigue.  Sometimes they’ll notice bruising or spots all over their bodies.  They’ll notice that their gums are bleeding easily when they brush their teeth or they have nosebleeds when they’ve never had them before. 

A fair number of patients actually present with an infection, so a sew throat that doesn’t seem to go away.  They get swabbed for mono, and the practitioner sees these weird cells in their blood, and they think, well, maybe this is mono because they’ve had fatigue, sore throat and some lymph nodes, and so that’s the way people present. 

Sometimes people present really sick, with a pneumonia or another infection, and then that’s when you go to the ER and you come into the hospital and it’s like, oh, wow something else is going on. 

 

Andrew Schorr:

Okay.  So they get to you, let’s say, at Oregon Health and Sciences in Portland, a major university center, and you run this genetic panel.  Now, it’s seven days.  So, first, what’s going to happen while you’re trying to figure out what version of AML they have and whether you have a therapy. 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

So let’s just talk about that.  What happens first, and then based on the information what happens then? 

 

Dr. Borate:

So it really depends on what you said before is how sick you are and what type of AML that you have.  So I would say even now about 30 percent of our patients don’t come through the ER and are not that sick.  They come through an outpatient clinic appointment where they’ve had low blood counts, they’ve been tested, there’s some testing that is done which indicates they may have leukemia, and they actually come to my clinic. 

And if they come to my clinic and they’re relatively what we call stable we will perform all this workup, as we call it, as an outpatient.  So we’ll to the bone marrow biopsy as an outpatient.  We will let them be at home for those seven days so they can sort of start preparing for, hey, maybe there’s something going on and this will need some length of treatment in the hospital or multiple visits to the physician, in which case if you’re working you need to start thinking about time off and preparing, and if you have kids how to they get to their activities.  So all the different things that people are struggling with when they get this diagnosis.  So that is about 30 percent of patients.

And in those seven days while they’re waiting, sometimes it’s longer, we keep a really close eye on their blood work.  So if they live close to a hospital or a clinic we make sure they go to the clinic at least two or three times a week to see what their white blood cells, platelets and red blood cells are doing, and then we get those results.  So we monitor them before they come back to get the final diagnosis and what their position is. 

If it’s somebody like Don who ended up in the hospital really sick, then they stay in the hospital while we’re doing this testing.  Typically they will get blood.  They will get platelets.  They would get what we call a workup, meaning we will check their heart, their kidneys, their liver.  We would put what we call a central line, meaning a line or an IV that can stay in their bodies for a longer length of time that can allow them to get treatment and allow them to get blood work and transfusions.  So all this is happening in the background while we are figuring out the subtype of AML. 

The other thing that we also do at that time is we collect what we call HLA typing, and this is to figure out what the tissue type of the patient is.  So like Don, when he went on to the transplant it’s really important for us to know this beforehand.  So while the patients are getting treatment in the hospital we can see if they have matches.  So does your brother or sister, can they be a match for you to donate bone marrow, or does it have to be somebody through Be the Match, as Don said, would that‑‑would it be what we call an unrelated but matched donor that would then be an option for you in the future. 

 

Andrew Schorr:

Okay.  So now the testing comes back.  This next generation sequencing, which is so cool now to see your cancer genes, what cancer genes are active, what could be driving your acute myeloid leukemia, and it says this gene.  And I know they have a lot of different letters, IDH, FLT3.  You could probably name a whole bunch others that different drugs have been developed for.  So it comes back with this letters and you say, ah‑ha, if we have a drug that targets that we can tamp this down.  Right? 

 

Dr. Borate:

Yep. 

 

Andrew Schorr:

Are these drugs infused?  Are they pills?  My understanding is now you have some pills that people can take as well. 

 

Dr. Borate:

So I think that’s one of the really cool things moving forward is most of these new targeted agents are actually oral, so medications, so pills that patients can even take at home to treat their leukemia. 

So just to back up a little bit, once we get back this genetic testing and we know their mutations and like you said IDH1, IDH2, FLT3, these are all mutations that can be targeted, we also determine a little bit‑‑and this can be somewhat arbitrary but is determined more by the patient, their age, their ability to, you know, how able are they to do their day‑to day activities?  Are they somebody who really is not even able to go to the grocery store without being really tired?  We call it, for lack of a better word, performance status.  How do they do in their everyday life? 

So we take all these factors to consider two broad categories:  Is the patient what we call fit versus, and I know this is not the kindest word, we call it unfit.  And I think those broad categories then lead us to what type of therapy should the patient get.  Should they get what we call intensive induction, meaning we still give them very broad chemotherapy to kill all the leukemia, but now we’re adding targeted therapy to the chemotherapy so that you give this double‑whammy?  You knock them with chemo, and you knock it also with the targeted therapy. 

However, if you happen to be 85 and you’re a very functional 85, maybe, but you’re not somebody whose organs can tolerate this heavy intensive chemotherapy or a transplant in the future, then we go with what we call more therapy that’s what we call less intense even though it might be IV, but then we add these targeted agents which they can take at home as a pill and then they’re not in the hospital as much.  They get this therapy as an outpatient while they’re getting treatment for their AML.  So it’s very different based on our goals of care, the patient in front of us and what mutations they have. 

 

Andrew Schorr:

Okay.  So increasingly now you may‑‑maybe somebody would get some chemo, working on approaches where you don’t lose your hair. 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

You don’t develop mouth sores. 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

Or ad nauseam.  You’re working a lot on lowering the toxicity. 

 

Dr. Borate:

Correct. 

 

Andrew Schorr:

And, Don, I know you went through that you’re being prepared for a transplant, heavy‑duty.  But that’s been ameliorated to a greet degree for many people. 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

And then somebody may be on a pill.  Now, do you have a growing range of treatments so if you try one and it doesn’t work or it doesn’t last you have something else?  It’s kind of like an antibiotic.  The doctor says we’re going to try this antibiotic.  No.  Your swollen glands and lymph nodes, it’s not going away.  Let’s go to this one. 

 

Dr. Borate:

We absolutely do.  And I think that’s sort of the next frontier is what we call sequencing.  How do you sequence treatments so that you can continue to get a good response even when the patient fails a treatment and the leukemia decides or figures out how to outsmart that treatment?  And unfortunately that still happens even with targeted therapies that over time the leukemia figures out a way to survive despite a very targeted approach.  And so how do you come back in with a different drug that can still work?  And how do you sequence those drugs to give them maximum effect but the least toxicity as you said, to the patient?  And those are sort of our next frontiers of clinical trials and therapy. 

 

Andrew Schorr:

So at this interim stage, Dr. Borate, one key question:  Don talked about the statistics, which were not good when he was diagnosed. 

 

Dr. Borate:

Yeah. 

 

Andrew Schorr:

Are you seeing a change in quality of life, and you believe in survival based on everything you’re talking about? 

 

Dr. Borate:

Yep.  I’ve seen a huge change in quality of life.  And I will say interestingly in AML more than any other disease we have really pushed this aspect in our older patients.  Because we have heard loud and clear from patients who are 70, 75, 80, that they want to live.  They want to live as long as possible, but they also don’t want to spend all that time in a doctor’s waiting room in or the hospital.  They are very, very determined to have a good quality of life and enjoy whatever it is that they want to do. 

And I think we have really worked hard to deliver that with our targeted therapies, and I want to say the results are astounding.  I have an 89‑year‑old right now who celebrated his birthday and has been outpatient for the last year since his diagnosis.  An 85‑‑oh, an 86‑year‑old, and we celebrated her birthday on (?) Inaudible where she took a pill for 13 months and is in remission and is talking about taking a trip to Bolivia. 

So to me these are huge success stories for my patients because I have a soft corner for my older patients.  They have struggled, they have sort of supported their kids their whole life, and it’s their time now.  And I think that’s so important to deliver that to them. 

 

Andrew Schorr:

Well, Dr. Borate, first of all, thank you for your devotion to patients.  We’re going to talk more about treatments.  We’re going to be taking your questions from our audience along the way, aml@patientpower.info. 

Don, you have been in Team in Training with (?) Inaudible, run I don’t know how many marathons, and it’s for research.  This must make you feel good that research is paying off. 

 

Don Armstrong:

On this side of the screen I am smiling so, so huge, and I’m actually very emotional about it.  It’s great to hear what Dr. Borate is saying because it gives other people a lot of hope and encouragement.  It’s just great to hear because it was not an experience that I would want anyone to go through, and so these are big moments.  So thank you, Dr. Borate, for what you’re doing. 

 

Andrew Schorr:

And if mom and dad want to go Bolivia or Thailand or Europe or wherever it is their time, as you say, Dr. Borate. 

 

Dr. Borate:

It is their time. 

 

Andrew Schorr:

So, Amanda, let me go to you.  So the Leukemia & Lymphoma Society has lots of services.  Some of it‑‑and your cat’s going to help us too, there‑‑is first of all getting information.  Where can I or mom or dad or grandma or grandpa, Uncle Charlie get the right care, okay, state‑of‑the‑art care?  But also then as we get to some of these treatments then they say, oh, my god.  There’s all this medical care and medicines coming in, and there’s expense.  So you all help people with that, too, right? 

 

Amanda Fowler:

Yes, absolutely.  We hear all the time how expensive treatment can be, and these new drugs are amazing but they do come at a cost.  So we have various different options to help patients through a program like copayment assistance that’s available most of the time but is subject to availability.  So we encourage people to call us.  And if there’s something that we don’t have we will work with the patient to find other options. 

It is a big burden to people, and it’s certainly one of the things that people worry about the most.  And this does often come from the caregiver because, like we said, the patient may be feeling pretty ill or be in the hospital, so we just encourage you to call and see what’s available. 

 

Andrew Schorr:

Okay.  Yes, I know.  I take an oral therapy for another leukemia, chronic leukemia, and I’m on Medicare, and I have Medicare Part D and I have a substantial co‑pay.  Now there are foundations, the Leukemia Society, that depending upon your need can help.  And if you’re on commercial insurance and you’re younger and not on Medicare there are other programs that come into play, right, Amanda? 

 

Amanda Fowler:

Yeah.  We will talk to patients, whether it’s through a nonprofit like us or through the pharmaceutical company directly.  And I certainly encourage people when they’re making that transition to Medicare, which often they know about in advance, to call us and we can help talk to you about ways to make that transition a little bit easier because you do find that the cost out of pocket to the patient can sometimes go up when they make that transition. 

 

Andrew Schorr:

Okay.  Dr. Borate, I have questions for you.  Maybe you is tilt your screen down a little.  We’re just losing you.  There we go.  There, that’s good. 

Dr. Borate, so you mentioned clinical trials.  We talked about research.  So you’re doing clinical trials, and many of your peers at other academic medical centers are doing clinical trials, and that’s what led to the approval of these drugs by the FDA based on data that you as researchers and drug companies and National Cancer Institute were able to present.  So talk to us a little bit about what’s in the lab, if you will, that you may be offering patients in clinical trials.  And then we’ll also understand, Amanda, when somebody is in a clinical trial what costs may be covered, too, okay?

So, Dr. Borate, first, what’s going on in research? 

 

Dr. Borate:

So I think, as you said, clinical trials really pave the way to new therapies.  And again I want to have a special acknowledgment and shout‑out to all the patients and their families who participate in these studies because it is a little bit of a leap of faith.  You know, sometimes we’re not always sure these treatments will work and they have side effects, so for patients to put their trust in us and sign off for these studies is I think a big deal.  So thank you. 

When we start somebody on a clinical trial we always collect what we call a pretreatment sample.  So we’ll get a sample of their disease before they’ve had any treatment, and then along the way as this treatment progresses we get multiple what we call post‑treatment treatment samples, one to look at the status of their disease, and secondly to send the sample then back to the lab to understand how these new treatments are affecting the disease.  You know, what pathways in these leukemia cells are being inhibited so that the cells are dying?  What pathways are deactivated, which also helps the cell to die? 

And then thirdly, what pathways are being sort of turned on to help the cell resist these treatments.  We call them mechanism of resistance and it’s similar to the antibiotic analogy you said where you take an antibiotic for a while and it seems to be working initially but then your body develops resistance to it and so the provider or the doctor has to change therapy because now this drug no longer works for your infection. 

And so the same thing happens with leukemia or any cancer, and I think it’s very important for us to observe the samples as the patient progresses through therapy so we can figure out, first of all, why it worked, but also why did it stop working or why did it not work.  And I think that’s where participation in clinical trials is so critical because without this valuable information we really can’t move the field forward. 

 

Andrew Schorr:

Okay.  Amanda, just about costs.  So if somebody signs up for a clinical trial might some of the costs be covered? 

 

Amanda Fowler:

Yeah.  It’s actually a bit of a complicated question, but generally speaking the cost of the actual trial drug is covered through the trial itself.  But it is important to talk to your insurance provider because hospital stays and some other supportive care may still go through your insurance. 

 

Andrew Schorr:

Okay.  So it’s complicated, but it’s something to discuss.  Dr. Borate, one other thing about testing.  So we mentioned somebody gets to the hospital, and ideally there’s this panel, this next‑generation sequencing done, fast track trying to get the results back to the specialist to decide do you have a targeted therapy or what’s going on, what’s your version of AML. 

But cancer is wily, and the cells can change, and the cancer gene that was driving your AML on day one could be different on day 50 or 100. 

 

Dr. Borate:

Absolutely. 

 

Andrew Schorr:

You would know the (?) numerical better than I.  So is retesting sometimes needed if something changes? 

 

Dr. Borate:

Yep.  So I think this is a great question, Andrew, and I think it ties into what Amanda said about centers of excellence because this is something we routinely do in our AML patients every time.  We sort of look back and see what their disease is doing, and we call it re-staging.  And sometimes we see certain genetic changes or mutations come in even when the patient is in remission.  When we can’t see the AML we can see some of the background cells acquire different mutations so we can keep a closer eye on the patient as they continue down the road.  So I think retesting is one of those things that is not done enough if you don’t have experience with the disease. 

Because you’re absolutely right.  The disease is wily.  It does change.  The mutation that was driving your disease to begin with may not be the one driving it when it relapses, and I think that’s really where we need more information, and we need to have this testing done in order to treat the patient appropriately. 

 

Andrew Schorr:

Okay.  So let’s go back to what leads to AML for a minute.  So Don, you worked on golf courses your whole life and eventually became the superintendent of one of the more famous PGA golf courses.  Colonial, is that right? 

 

Don Armstrong:

Correct, yes. 

 

Andrew Schorr:

In Fort Worth.  But over your years devoted to golf you sprayed a lot of pesticide, right? 

 

Don Armstrong:

I did.  I did.  From the time I was 15 years old I get my first job on a golf course and the superintendent knew I wanted to be in the industry, and so he let me do a lot of things that probably somebody else wouldn’t.  And one of them was spray the pesticides, pray the fungicides, herbicides.  You name it, I got to spray everything.  And back in that time frame the pesticides were a lot more potent.  We had a lot of mercury‑based, lead‑based products in those time frames that the EPA had not stopped in terms of use. 

And so I think back about whether that may have had an impact on where I ended up with the leukemia.  It’s hard to say.  I’m sure Dr. Borate would probably agree with that, but it seems to me there could be some correlation, yes. 

 

Andrew Schorr:

Probably so.  So environmental factors.  Dr. Borate mentioned hereditary to some degree.  And I want to ask about another thing.  I am not just living with chronic lymphocytic leukemia but I have another blood condition called myelofibrosis.  And some people with myelofibrosis progress to AML.  My understanding was this secondary version of AML was often harder to treat. 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

And I also understand, Dr. Borate, you’re researching it. 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

So are the options, is the chance for hope for people who developed this secondary AML? 

 

Dr. Borate:

So thank you for bringing that up.  I think secondary AML has always been this sort of thing that people don’t want to touch and especially when you’re looking at clinical trials investigating your new agent because we knew that, hey, if you were treating patients with secondary AML with a newer therapy maybe the results wouldn’t be as good and then your clinical trial results overall don’t look at good. 

And to me that is a huge disservice to our AML patients because, as you describe, either because you had a prior cancer, let’s say you had breast cancer and you had chemotherapy for that breast cancer or lung cancer and you survived it, and so you’re a survivor.  And 10 years later you develop AML as a result of exposure to prior chemotherapy, which in many ways does things to your stem cells like a pesticide that Don might have been exposed to.  (?) Sorry, I apologize.

And so I think the thing that secondary AML has taught us is when a patient develops secondary AML there is a large number of genetic mutations already existing in the patient from their prior chemo, from their prior cancer, from their prior exposures.  And so because the treatment is so hard it’s something that we’re looking about very carefully in the lab to understand it much better. 

And especially about secondary AML from myelofibrosis or these diseases we call MPNs, meaning myeloproliferative neoplasms maybe essential thrombocytosis, polycythemia vera, all these big names.  We have a study here at Oregon Health and Sciences University which combines our targeted therapy.  You might have heard about it.  It’s called Jakafi is the commercial name or ruxolitinib is the pharmaceutical name, and it targets a mutation called JAK or JAK2.  And then we combine it with a chemotherapy we call, just called Vyxeos, which has also been recently approved specifically for secondary AML. 

And so we’re taking that approach I describe where we’re combining the therapy that’s already on the market for secondary AML and has shown benefit, but then we’re adding this targeted agent which is also on the market for myelofibrosis but they haven’t ever been combined together.  But we’re doing it in a way that’s slow and careful and cautious because, you know, we have to talk about safety, and we want our patients to get the benefit but not the toxicity.  And we want to see what this does.  The response rates for secondary AML from myelofibrosis are anywhere from zero to 15 percent, which is terrible.  And so we really want to improve on that. 

 

Andrew Schorr:

Okay.  Let’s talk about transplant again.  So, Don, you went through a transplant, and I interviewed a transplant survivor years ago who did well afterwards, but he said, Andrew, it is not a walk in the park.  Now I know there have been a lot of refinements and you had it a number of years ago now, but what was the transplant experience like? 

 

Don Armstrong:

It wasn’t a walk in the park.  As a patient I think we hear what we want to hear, and I didn’t really hear about a lot of the side effects that might occur from having a transplant because I was so focused on just surviving.  I thought I had actually skated through the GvHD, the host‑versus‑graft disease resistance, until probably day 30 or so, and I started having presentation on my skin, and I started having issues with my throat, my eyes. 

So I had to go through all those additional struggles on top of fighting the initial treatment from the leukemia.  So it was tough, and it was something that, it was‑‑it’s difficult to be prepared for that because you’ve already been through all the chemo for the leukemia.  I was grateful that the stem cells did what they were supposed to do, which was graft in my body, but the side effects were difficult.  They made it quite a challenge. 

 

Andrew Schorr:

And you continue to take some medicine related to anti‑rejection? 

 

Don Armstrong:

No, sir.  I haven’t taken anything now probably for, for probably six or seven years. 

 

Andrew Schorr:

Good.  Good.  Dr. Borate, just so we understand with a transplant.  So you’re getting somebody else’s cells to‑‑you get the chemo to knock back the disease in your body, and then you’re having somebody’s healthy cells be infused to try to take offer the immune system.  My understanding is even your blood type can change.  I’m B‑positive.  I get somebody who is O or something that becomes my blood type, right? 

 

Dr. Borate:

Yes. 

 

Andrew Schorr:

So it’s a whole rebooting and a changeover, right? 

 

Dr. Borate:

Right.  I think the one thing I do want to clarify is you mentioned you get a lot of chemo to take care of the disease in your body, but most successful transplants are actually done when you’re in remission, so when the patient is in remission.  Because the chemo that’s given is really given to destroy your own existing bone marrow and immune system and to make a home and to make place for these new donor cells that will then come in and survive.  If you did not do that then your immune system and your bone marrow would immediately reject any of those stem cells that were being given to the patient. 

If you still have disease in your body and a lot of disease, and then you get all this chemo to prepare you for a transplant, the risk of rejection or the disease coming back is actually quite high because when you‑‑when you destroy your own bone marrow including bone marrow that has disease in it and then you infuse somebody else’s stem cells, you have a period of about two to three weeks when you have no immunity.  And the stem cells are trying to grow, but if the patient still has leukemia in their body or had disease when you started this process, those disease cells just grow out of control, and they kill all the donor stem cells, and then it’s just not a good outcome. 

So we really want the patient to have as less disease, preferably no disease in their body when they get a stem cell transplant.  And this is not something that is intuitive to a lot of patients because it’s seen as a treatment for AML, which it is, but you really want to give it when the disease is really under really good control. 

 

Andrew Schorr:

Amanda, could you talk a little bit about the support programs that the LLS, the Leukemia & Lymphoma Society, has, and Don I’ll have talk about it as well, so that somebody going through this, first of all they and their family have never heard of this before.  They don’t know anybody with it.  The treatments can be significant.  Hospitalization could be long or not.  How do you know you’re not alone?  Not just calling you on the phone but there are other resources you have too. 

 

Amanda Fowler:

Sure, absolutely.  I think, like you said, just knowing you’re not alone it’s really important for people both caregivers and patients to connect with other people who have been through this.  It’s very likely until diagnosis a person may have never heard of AML.  They just have a vague idea of what leukemia is.  So we have ways to connect patients and caregivers with other people. 

We have a wonderful program called the Patti Robinson Kaufmann First Connection, and that is a telephone peer‑to‑peer connection.  So we will match you with someone of a similar age and gender who has the same diagnosis and has already been through treatment.  And they are trained volunteers.  We also have in‑person family support groups.  We have online support groups, including ones specifically for leukemias, one specifically for caregivers as well as young adults. 

We also have an online community, so if you’re not available for the live chats you can post there and connect with people all over the world who have been through a similar experience.  While every patient’s journey is really unique there’s going to be some similarities where you can know that you’re not alone.  And I think all of these technologies are great because you can even connect while you’re still in the hospital. 

 

Andrew Schorr:

And, Don, you are a First Connection volunteer.  I’ve done it too, with people with my leukemia.  So you talk to people one‑on‑one. 

 

Don Armstrong:

That’s correct.  By the way, I do want to add that my blood type did change because of my stem cell transplant. 

 

Dr. Borate:

Of course. 

 

Don Armstrong:

You’re absolutely right, yeah. 

The First Connection program is probably one of the most rewarding things that I’ve done since my treatment and making it through that.  To be able to talk to another person that’s going through something that you went through and really just answer any questions they may have is really very rewarding, and I know it’s great for the patient as well. 

When I was going through treatment it was wonderful to hear the doctor say that you’re doing well, it was wonderful to have the support from the nurses, but I really wanted to talk to somebody that had gone through is so I could say, okay, tell me about it.  What was it like?  Did you have this problem?  Did you have that problem?  So it’s just a great one‑on‑one, as Amanda said, opportunity to help answer questions and hopefully give some additional encouragement to patients. 

 

Andrew Schorr:

I want to add some additional resources.  So, first of all, the originator of this program is a group called the Patient Empowerment Network.  Their website is powerfulpatients.org in partnership with the Leukemia & Lymphoma Society.  And we’ve worked with them many times at Patient Power. 

Most recently, we did also a program at the big American Society of Hematology meeting, and that’s where all the hematologists, like Dr. Borate, from around the world come and where research is presented and they talk about it.  This year there was a lot of AML, and so we sat down and had a discussion with peers of Dr. Borate’s, and that is Dr. Kadia from MD Anderson and Drs. Lee and Dr. Ritchie from Weill Cornell in New York, other NCI cancer centers like where Dr. Borate is. 

And so I urge you to take a look at some of these programs.  If you go to patientpower.info and just go to the leukemia and then the AML area you can see the replays of these.  So that’s another resource for you. 

And then I will tell you that some people are connecting on a platform like Facebook, and there are some AML groups there.  A couple of caveats we’ll give you about the internet.  I’m sure Dr. Borate warns people about Dr. Google.  First of all, some of the information sometimes when you just search is not current.  And you’ve heard for the first part of this program things are changing, right?  And it’s very nuanced.  And Dr. Borate may have a meeting with her colleagues tomorrow, and they’ll say, oh, well, now we know this.  So there’s no way some of these services can keep up, particularly just general web searches.  So be careful about that.  That’s why you need to call Amanda because she’s staying on top of that. 

The other thing I’d say is in Facebook you may go to an AML group, which is wonderful, people talking to one another, but we’ve talked about all these different situations in AML so one person’s situation may be different from another.  So there may be general support, but remember, we talked about it at the very beginning of this program, you need to talk to your healthcare team to get a clear picture of your or your loved one’s situation and have a plan that’s, in this age of personalized medicine, is right for you. 

And I’m sure, Dr. Borate, you have people come in sometimes with no information, but often you have people who come in who somehow have wrong information, and maybe you could talk about that, about how people‑‑how can they ask the right questions to get to the right answers. 

 

Dr. Borate:

I think you’ve touched on such an important point because, as you said, patients are scared, their caregivers are scared.  They’re looking for information.  There’s information that they getting from the providers or the physicians, but obviously there is this need to help their loved one and so there is a lot of Google searching, joining groups. 

Some of the big things that we see that are difficult is there’s a lot of information about supplements and alternative therapies, which while I think absolutely can help with many, many things including fatigue, nausea, feeling of well‑being, I think you have to be careful about what that resource is and what studies have been done on it.  So I think those are questions that we get a lot and we try our best to have evidence‑based data on these different‑‑they’re like medications because they are something you’re putting into your body and while some are more natural than others, for example, turmeric is one that is used extensively by people.  They do interact with some of the other treatments you might be getting for your leukemia. 

So just understanding how your supplements are interacting with the treatments that you’re being prescribed I think is important, and there’s some resources that can actually do this in a very evidence‑based manner. 

I think going to societies like the Leukemia & Lymphoma Society, we have the ASH, as you said, American Society of Hematology, ASCO, which is the American Society for cancer, these websites‑‑I think the NCI website, the national center for, you know, all cancers, they’re just really great resources that tell you what you’re up against in a very sort of patient‑friendly way that explains the treatment. 

And I think something that you guys discussed before, the First Connection resource, I think that is something that‑‑I mean, it’s a resource that is so underutilized because even as a provider who treats AML for many years I don’t have the experience that Don had.  I didn’t go through a transplant.  I didn’t go through GvHD.  So while I can discuss side effects I can’t really present a patient’s perspective, and that’s what they are looking for a lot of times.  Just looking at a role model or reassurance that this is what a patient or somebody who looks like me went through and came out on the other side.  And, yes, it wasn’t a walk in the park, and, yes, it was awful at times, but he came out on the other side and this was what he needed to do that.  I think that is so valuable. 

 

Andrew Schorr:

Right.  Just one aside.  GvHD.  You hear all these acronyms.  Graft‑verse‑host disease, where those new cells from somebody else are fighting with your immune system.  They’re going to win because they did for Don, but it’s a fight, and you have side effects with it that could continue for a long time. 

Amanda, what questions‑‑I know it varies by where somebody is in their journey with AML, but what questions do you suggest to people that they ask their doctor or a new center that they go to so that they or mom or dad get the right treatment? 

 

Amanda Fowler:

Sure.  I think that’s actually a big part of what we do in the Information Resource Center is talk to patients about what to ask the doctor.  We can’t always answer their questions, particularly specific medical ones, but we help them get (?) Inaudible to rate that list out to what’s most important to them. 

It really does depend on the (?) fees of where they are on their treatment, but an important question, something that Dr. Borate alluded to earlier, is what the goal of treatment is.  Is my goal curative, or is my goal to extend my life for as long as I might be able to?  Because people are on that borderline sometimes of fit and unfit, and they need to understand which type of drugs the doctors are prescribing for them and why. 

And then of course the question of am I a transplant candidate, why is why not?  I encourage people to ask why because they may think I’m a great candidate and the doctor says well, actually you know, your cardiac function is very poor and you won’t be able to survive a transplant.  I think it’s good for peace of mind to understand the reasons doctors are making these decisions for them. 

 

Andrew Schorr:

Amanda, what about second opinions?  So even if you’re in a major city there could be one big hospital over here and one‑‑I think like New York.  There are more than one NCI cancer center.  So what about that?  What do you tell people about that? 

 

Amanda Fowler:

Absolutely.  So AML can be unique in that sometimes there isn’t a chance for a second opinion upon diagnosis, right?  Sometimes they go in and they need to start chemo right away.  But generally there’s next phase.  There’s a maintenance phase or there’s a transplant phase.  Great time for a second opinion.  I’m a huge believer in second opinions.

With the way treatment is evolving there’s options now.  Really there used to be, like we said, for 40 years there was one option.  Now there’s many, and so you want to be sure that you’re comfortable with your choice, comfortable with your physician because this is going to be a long journey.  No matter whether you have transplant or not this is something‑‑it’s a long relationship, and so we encourage you to call us and we can help guide you to those centers of excellence.  Even if you’re at one you may want to talk to a second one as well. 

 

Andrew Schorr:

Okay.  Dr. Borate, you are a specialist so you’re at a center of excellence.  But how do you feel if somebody or a parent or family member says, you know, we’re going to go over here and see what they say.  Are you okay with that? 

 

Dr. Borate:

So I think any physician or provider who takes care of patients should really be okay with that because we’re all in this for the same reason and that’s to make our patients better and hopefully cure them.  And I think the way we get there shouldn’t be something that you worry about what one person says versus the other.  So absolutely. 

I do agree with Amanda that sometimes for AML, and fact a majority of times for AML when the diagnosis is made time is of the essence, so unfortunately sometimes our patients don’t have the luxury of being able to go for a second opinion or get a second opinion simply because they’re so sick.  They’re in the hospital.  Their disease needs to be treated right away. 

But I completely agree, once that first step is done I think taking a pause, talking about different options with your current physician and then saying, hey, do you mind if I go to the next center?  So for example we’re close to Seattle or California.  Just taking a flight and having a conversation and usually the second opinions really reassure the patients and the caregivers that they’re on the right track, and so they can come back to their original center and continue their treatment. 

The one caveat I have to a second opinion before starting therapy‑‑or after starting therapy, rather, is once you’ve already received a therapy for AML you may not be eligible for a clinical trial for newly diagnosed AML patients.  So we do have patients that come to us after having several cycles of therapy and then want to participate, and unfortunately the way trials are designed you want to get all the information right from the beginning, and so that’s when you enroll on a study when you’re starting your treatment. 

With that said, I mean, it is what it is sometimes just because of the rapidity of the disease and the symptoms, but that is if you’re considering a clinical trial very strongly you may want to go to a center of excellence sooner rather than later.  

 

Andrew Schorr:

One other point I want to make about clinical trials, because I’ve been in two, and about second opinions actually, is don’t drive yourself crazy.  Dr. Borate, and maybe you go to another center, you go to Seattle up the road or California down the road.  And then you say oh, no, now I’m going to the Mayo Clinic and then I’m going to Northwestern and then I’m going to New York, you will go crazy, and you will probably start hearing the same thing, right?  As well as you went through a lot.  So pick a team. 

Amanda, any comment you want to make about that?  Because I’m sure you have people, they’re very stressed out. 

 

Amanda Fowler:

I agree.  There is a number of second opinions that’s too many.  But I also wanted to say on the clinical trial piece we at LLS have a wonderful service called the Clinical Trial Support Center that can help you find those trials.  It’s a team of nurses who do individualized trial searches for people. 

Sometimes that can help inform where you go.  If you’re debating between California and Seattle and our nurses narrow it down and say, you know, there’s a trial in Seattle you could be interested in, it might help inform where you actually go for your second opinion.  And you would reach them the same way you would reach me, through the Information Resource Center. 

 

Andrew Schorr:

I want to recap just a few key points for our audience, and then get some closing comments from everyone.  So, first of all, remember what you heard at the beginning.  You want to, with the help of the Leukemia & Lymphoma Society, you want to get to where they’re really knowledgeable in this changing landscape of AML.  You want to be tested or your loved one so that you know what version of AML you have.  And if things are changing now that treatment has gone on for a while, retesting to say what’s going on now, and consider all your options. 

And Amanda said it just a few minutes ago, so important, discuss your goals for treatment.  What kind of life do you want to have?  Do you want to just knock it back, take pills at home?  Do you want to go to a transplant if you’re qualified for that?  You know, these are all the things to discuss with a knowledgeable team. 

And consider a clinical trial.  And connect with Don or his peers around the country as First Connection people.  So just a few key points.  So first of all, Amanda, what do you want to leave people with?  Probably call the LLS, right?  Call. 

 

Amanda Fowler:

Absolutely.  You know, if you have any questions give us a call.  We’re happy to help.  We’re there to talk to you and help find those important resources that you need.  And also just what a hopeful time it is for AML.  When I started at LLS there had been nothing, and now, as Dr. Borate has said, there’s nine new drugs and (?) evolving quicker than we can almost keep track.  So it’s a really hopeful time right now. 

 

Andrew Schorr:

Okay.  Dr. Borate, first of all, we all want to thank you to you and your peers around the world who are doing research, but a final comment you want to say to this audience and family members and patients who are so worried about this diagnosis. 

 

Dr. Borate:

I do want to echo what other folks have said.  This is a specialized disease, so reaching out to a center that has experience is I think critical.  Even though we might not be able to physically travel at least getting advice from that center, whether it be through your physician or in‑person. 

Secondly, I do want to say participating in clinical trials is a wonderful way not just to get treatment but also to get access to new drugs that could benefit you.  And the other part of a clinical trial that’s never discussed is just by being in a clinical trial you are monitored way more closely and observed way more closely than if you were not on one just because that’s what a clinical trial mandates us to do.  And I think the experience of our patients who are on it is always satisfying, whether the trial is helpful or not.  Just the close connection and the follow‑up that they get is just‑‑it’s a great way to be supported through your therapy. 

And the last point I want to make is something that Don said.  You need a support system.  You need your family members.  Don’t be shy about calling your sister in Florida or your father or mother that live half‑way across the country from you.  This is what family is for.  Surround yourself with your family and friends.  You need it.  You don’t want to do this alone.

 

Andrew Schorr:

Right.  And also remember for you as a family member, there is support for you too.  Leukemia & Lymphoma Society can help.  There are other groups.  The cancer support community on Patient Power.  There’s a care partner section and even with First Connection volunteers there may be some who can help the family as well.

Amanda, thank you so much for the work you do.  Don, final comment from you because here you were treated in 2005 and then took medicines for a while, and you get to speak, but you learned lot today.  Hearing all this what do you want to say to our audience? 

 

Don Armstrong:

I just want to say just be encouraged by all the great new technology that’s come down in the last several years.  Be encouraged by that.  I also want to add to ask a lot of questions.  Make sure that the time you spend with your doctor is quality time.  Don’t let the doctor leave without a question being answered that’s on your mind.  And third, use the resources that are out there that can really benefit you like the Leukemia Lymphoma Society IRC. 

 

Andrew Schorr:

All great advice.  I want to thank everybody for sticking with us.  Remember, there will be a replay of this program.  There will be all sorts of video clips.  There will be a transcript.  All that coming your way.  So look for that. 

Also look for these earlier programs that we’ve produced with support from the Patient Empowerment Network and with the Leukemia Society that really will even broaden your knowledge. 

But we had some great information today.  I want to thank our guests.  I want to thank you for being with us.  I want to thank the companies that have been devoted to research with the physicians like Dr. Borate who have been supporters of this program, Celgene, Daiichi Sankyo, Jazz Pharmaceuticals and Novartis for their support and devotion to the leukemia community. 

And remember, please consider clinical trials in this fast‑changing field as they’re learning to combine medicines.  Does that help you or mom or dad, grandma or grandpa, so they can live a longer, better life?  In Los Angeles with our friends who have been in Colorado and in Texas and in Portland, Oregon, and wherever you are, 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.

Medication Maintenance Tips for Caregivers

Managing medications can be difficult to do, especially if you’re a senior caregiver. Helping someone else remember to take medications on time and work to find the right balance for them can seem like a daunting task. Thankfully, we’ve got a list of tips and tricks to help make things flow more smoothly.

Make Sure Providers Are Aware Of Vitamins And Supplements

Medical providers should be aware of any vitamins and supplements a person is taking. Regardless of how natural they are, they can interfere with medications and other treatments. For example, someone on blood thinners should not be taking a supplement with vitamin K. Most blood thinners work by inhibiting the production of this vitamin in the body. Taking a vitamin K supplement can negate the work of blood thinners.

Instructions

Make sure to go over medication instructions with the senior you’re caring for. If they are able to, they should know the names of each medication along with dosages and what times to take them. It doesn’t hurt to type up instructions about medications so that all information is in one place and easy to access. Consider adding in what side effects they should seek help for. That can serve as a list for caregivers and seniors to check on in case of adverse events.

Alarms

Set alarms to remind seniors to take their medications. There are many options to choose from. Smartphones allow you to set up reminders with different sounds each time which can help people differentiate between medication doses and other alerts. Electronic personal assistants like Alexa or Google Home can easily be used for reminders as well. If the senior you’re caring for struggles with newer technology, consider a few alarm clocks around the home.

Keep A List

Keeping a list of medications can help seniors and caregivers alike remember what medications are due at what time. Lists that have both a visual of what the medications look like and allow people to check off a medication dose can be useful tools. If you’re going with this kind of list, make sure that you have multiple copies. Placing one next to a pill organizer and another on the fridge can help remind people to take medication before they’ve even missed a dose.

Smartphone apps can also be helpful in tracking this information.

Follow Up

It’s important not to just set alarms or reminders, but check in to ensure that someone has taken their medication. It can be easy to turn off an alarm and still forget to take medication as scheduled. Following up with the senior in your life can remind them that they didn’t take their most recent dose.

Store Medications Properly

Most medications do best when stored between 68 and 77 degrees Fahrenheit. Additionally, many of them need to avoid humidity, direct sunlight and more. Medications should not be stored in vehicles, on windowsills or other sunny and warm spots or even in the bathroom. Consider storing them in a cool, dry space in the kitchen or living space.

When medications aren’t stored properly, it can affect their potency and make them potentially dangerous. If you’re concerned that your senior’s medications have been affected, here’s what you need to watch out for:

  • Odd smells
  • Discolored pills, tablets and injections
  • Cracked or crumbled pills
  • Pills and tablets that are stuck together
  • Creams and ointments that show separation
  • Cloudy injections

If you see these signs, contact your senior’s pharmacist as soon as possible.

Sort Medications Into Pill Organizers

Set aside time each week to go through the medication your senior takes and place them into pill organizers. These can make it easier to remember to take medications as prescribed or even transport them while traveling. Some organizers can remind people to take their medications and even alert others that a dose has been missed.

Make Sure All Caregivers Know About Medications

A sure way to have seniors miss their medication doses is to have senior caregivers who aren’t on the same page. Without everyone being in the know, it becomes increasingly difficult to set reminders and follow up with seniors about medication doses.

Plan Ahead For Refill Needs

Refills may come up on days where a senior is alone. When that’s the case, they may forget or be unable to pick up their refilled medications. Refills may even be due when someone is planning to be out of town. Make sure to plan ahead adequately for refills and work with a person’s pharmacist.

Consider Compounding Medications If Needed

Compounding is a process where medication is tailored to a person’s specific needs. This can help remove any dyes a patient is allergic to or turn a pill into liquid for those who struggle with swallowing pills.

Get Tips from A Medical Provider

When methods to help your senior aren’t working as well as you had hoped, take some time to check in with their medical providers. Nurses have amassed a wealth of information on improving their patients’ quality of life. They are likely to have some ideas on how to make managing medications more effective.

Always Communicate With Family Members

Whatever steps you take to maintain a senior’s medication schedule, make sure that you’re communicating any difficulties with the senior’s loved ones. Family should also always be aware of any medication changes. When so many seniors rely on a variety of paid and family caregivers, it’s incredibly important for everyone to be in the loop on the storage, administration and organization of all medications, vitamins and supplements.

Emerging Research and Promising AML Treatment Approaches

Downloadable Program Guide

Leading experts shared recent breakthroughs in AML treatment and research announced at the 2018 American Society of Hematology (ASH) annual meeting. The panel discusses new drug approvals, emerging clinical trial data, innovative, individualized approaches to treat distinct AML subtypes, and how these advances translate to the real world and impact AML patients.


Transcript:

Beth:

Hello, and welcome to today’s webinar. I’m Beth Probert. I am an MPN patient, was diagnosed a few years ago with polycythemia vera. Today’s webinar is where are we headed with the treatment of acute myeloid leukemia. What can patients look forward to for the coming year?

This is a Patient Empowerment Network program. And I’d like to thank our sponsors. As always, our sponsors have no editorial control over the content. Today, we’re going to talk about topics like recent breakthroughs in AML treatment and research announced at the 2018 American Society of Hematology ASH Annual Meeting. We’ll look at emerging clinical trials and how to access them, individualized approaches to treat distinct AML subtypes, and how will these advances translate for patients. You’ll also hear from AML patient Steve, as he shares his first-hand experience facing AML and how he’s doing now.

We will also answer viewer questions. And if you have a question, please keep in mind, we can’t get real specific with these questions, so try to keep them general, really geared more towards information and questions.

And we’d like you to send your questions throughout the program. We will try to answer all questions that come through. And if we can’t get to all of them, we will certainly address them through future webinars. Now, I’d love to introduce you to today’s guest. Our first guest is Dr. Naval Daver, associate professor, Department of Leukemia at the University of Texas MD Anderson Cancer Center. Welcome, Dr. Daver. I’m so glad you could join us today.

Naval Daver:

Hello. Thank you for having me. Glad to join.

Beth:

And our next guess is Leah Szumita. And Leah provides clinical trial support at the Leukemia and Lymphoma Society. So, Leah, thank you. I’m glad you can be here today.

Leah:

Thank you. I’m so happy to be here.

Beth:

And our next guess is our patient panelist, Steve Buechler, and he is an AML patient who has had a remarkable journey. Steve, welcome from Minnesota.

Steve:

Thank you. I’m happy to be here.

Beth:

Great. Well, Steve, we’d like to get started with you. I’d like for you to tell our viewers a little bit about your life with AML. And if you can include how did you get diagnosed, what was that like getting diagnosed, and how did you react, who is your support team, and just what you’ve been though. So, I’ll turn it over to you now.

Steve:

Well, at age 64, I was living what I thought was a normal, healthy life. I had no symptoms. My primary care physician had been monitoring my white blood cell count for a couple of years because it was borderline low but not too alarming. And then, in the spring of 2016, it began to drop more precipitously.

So, he recommended I see a hematologist, and I went to do that. And the hematologist said I should probably have a bone marrow biopsy. And so, I agreed to do that sort of to humor them because I didn’t feel sick. I didn’t have any symptoms. I didn’t have any idea anything was wrong. It was a memorable week. The biopsy was on a Monday. On Tuesday, I swam my normal 50 laps. I did some shopping. I ate dinner out. Wednesday morning, I played in a weekly poker game with some retired guys. So, life was normal, until that phone call that came Wednesday afternoon informing me I had acute myeloid leukemia, and I had to get to a hospital right away.

So, the next day, I checked into a hospital. The day after that, Friday, I started chemotherapy. So, in 48 hours, I went from feeling perfectly healthy to 24/7 chemotherapy drip. And they started me on this standard treatment that’s been use, I think, for a very long time called 7 + 3 Cytarabine and Daunorubicin to try to get the cancer into remission. And so, I spent a week on that medication.

And then, I waited for the inevitable drop in my white blood cell count and my immune system. I was going to be very vulnerable to various kinds of infections. And as predicted, I came down with colitis and an E coli infection, body rash, and a bunch of other stuff that they couldn’t even identify. But the infectious disease doctors stepped in and dealt with those issues one at a time. So, I ended up spending 5.5 weeks in the hospital for my counts to recover. But the good news was, one month after starting chemo, they did a bone marrow biopsy that found there was no residual leukemia. So, the first goal had been reached, at that point. I was in remission.

Adding to the story, of course, the first night I spent in the hospital, my wife was with me and left late in the evening to go home. And as she arrived home, she had a stabbing pain in her right leg. The next morning, she got up and could hardly get out of bed, called 9-1-1. They brought her to my hospital in an ambulance through the ER.

And it turned out she had a fractured femur. So, I was on one floor of the hospital in the chemo ward, and she was on another floor of the hospital awaiting subsequent surgery to repair her leg. And then, she went off to a transitional care unit for rehab. So, when I realized our house was going to be unoccupied for about a month, I started to write to our neighbors on email. And I found it was a really useful way to communicate. So, I ended up, over the many months that followed, adding maybe 60 people to that email list and sending over 60 emails out, over the course of a year and a half to keep people informed of what was going on.

I, subsequently realized, as I was writing for other people that I was really using that writing to make sense of my own experience. I struggled to figure out what was going on and how I could capture it and how I could explain to people. And it was useful to get their responses back, but it was useful for me. It was very therapeutic for me just to have that writing experience to make sense out of what was going on.

After 5.5 weeks, I got permission to leave. I went home for a while. But I was awaiting the genetic testing of my cancer to figure out what the next round of treatment would be. Because I think people know, with AML, there needs to be a second arm of the treatment. It can come back very fast and very ferociously. I was told that the genetic testing of my cancer would put me in either a low risk or a high-risk category for recurrence. And that would point towards either chemotherapy, if it was low risk, and stem cell transplant, if it was high risk.

When the results finally came in, they said, “Well, you’re kind of in an intermediate category.” So, the way forward was not as clear as I thought it might be. So, I talked to my initial oncologist. I did my own research. I, subsequently, went and talked to a transplant oncologist at the University of Minnesota Medical Center who sort of nudged me towards the transplant option. I went to the Mayo Clinic and got a second opinion. And all of the indications really were that I would be a good candidate for transplant. I had no comorbidity. I had no other health problems.

And everybody thought I should probably be able to withstand the conditioning fairly well. So, eventually, I came around to that decision to have a stem cell transplant. I had a brother who was a half match donor. But the folks at the BMT unit said we also have some good umbilical cord blood matches for you. And so, I was, again, faced with the decision about which way to go. But it turned out they had a study. Don’t they always have a study? I was randomly assigned to the cord blood donor option. So, my brother was off the hook.

And I ended up having a double cord blood stem cell transplant in October of 2016, about four or five months after I was initially diagnosed. That procedure went very smoothly. And within three weeks, a biopsy revealed that one of my cord donors was 99% engrafted, which is pretty early for a cord blood procedure. So, that was good news. I was able to go home, at that point, and begin a pretty long, extensive, and sometimes arduous process of recovery.

The first 100 days, they offered me to come back to clinic daily for the first month or so to get blood tests, to get platelets, to get red blood cell transfusions, whatever it is that you need to keep you healthy. It’s a pretty vulnerable time. One of the oncologists, at the transplant unit, described this whole procedure as, first, we bring you to the brink of death by killing off diseased immune system. And then, we try to bring you back again. Well, it worked, in my case, I’m happy to report. So, by early 2017, I was beginning to taper off my anti-rejection medication. That ended in April of that year.

And then, it was just a process of gradually getting more strength, getting better. And, in my case, very fortunately, I avoided any trace of graft versus host disease. So, that allowed me to have a pretty healthy recovery. One year after my transplant, of course, I had to go in and get my baby shots, my vaccinations and needles because my previous immune system had been obliterated. And they only gave me the dead vaccines, at that point, because they reasoned I couldn’t handle the live ones.

So, that happened at Year 2. And that was recently completed about two months ago. I got the rest of my vaccines. The other good part of the story is, although there was a 60 to 70% chance of graft versus host disease, I never had any trace of that. I’ve since become very active in talking with other patients as a volunteer, doing some writing, becoming involved in the cancer community. And I’ve come to appreciate really how fortunate my story was. I think the three big indicators were I got into remission on the first try. I’ve talked to a lot of patients who haven’t been able to do that.

My transplant engrafted within three weeks, which was a very solid, early result. And a lot of patients don’t have that kind of success. And I had no graft versus host disease. So, that’s about as good of a story as you can have with AML, as I understand it. So, obviously, I’m very grateful to have done that. And something like that gives me a lot of motivation to try and give something back. So, I’ve been participating in various ways in the cancer community.

Believe it or not, that’s the short version.

Beth:

Steve, you have a remarkable story. I just heard – we talked earlier, and just to keep hearing your story again is really just so noteworthy. And the three points you made, just having the early remission the first time with chemo is amazing. And early engraftment just within three weeks and no graft versus host disease. And your enthusiasm and wanting to give back and just with your writing. And we’ll talk a little bit later. I know that you have a book that’s coming out. So, your story is, for someone like me, amazing. But Dr. Daver, I’d like to turn to you, for a few moments, and tell me, is Steve’s story typical?

And what kind of feedback do you have on his journey?

Naval Daver:

So, Steve’s story is a very good outcome story. It’s not necessarily typical, as Steve mentioned. About 70 to 80% of our patients will go into remission with the first induction. So, it’s a high number, but it’s not 100%. And if you don’t go into remission with the first induction that is actually one of the very high risk or adverse features. It’s called primary refractory AML. And those patients usually do have a much harder time. The second thing is about 60% of patients will fall in what we call intermediate groups. So, we do do molecular and cytogenetics. And if we find that we have favorable molecular cytogenetic changes, then, those are considered to be good.

And we may not do transplant. On the other hand, if you have unfavorable cytogenetic molecular, then, it’s very clear a transplant probably is the only hope for long term survival. But, unfortunately, a lot of patients fall into intermediate group.

Now, that intermediate group is becoming smaller and smaller because we are understanding more and more about the molecular machinery, the cytogenetics, and the prognostic impact of new molecular mutations. So, we are able to triage patients better into high risk or low risk, which helps us make the transplant decision. But I think the most fortunate thing, in Steve’s case, was the lack of GVHD. And that actually is very uncommon. Most of the patients we see will have some degree of GVHD. It may be acute. It maybe chronic. In most cases, I will say that it is manageable. We rarely see very severe ICU requiring GVHD or fatalities from GVHD.

But about 60 to 70% will have some degree of GVHD, will require some treatment for it with steroids or additional immunosuppression. And in some cases, it can take many months and can be a major discomfort and affect quality of life. So, I think that was fantastic that he did not have the GVHD. And I think all of those features, although are seen in a traditional AML story, I think Steve was fortunate, and the outcome was very favorable so far.

Beth:

Great. I really like that feedback. And what I wanted to ask you, as well, in regard to the no graft versus host disease, you said about 60 to 70% will actually encounter that. So, am I correct in assuming then that, when you do a transplant with someone, you account that that’s probably going to happen, the graft versus host disease and you have treatments and things lined up in anticipation of that happening?

Dr. Daver:

Yeah, absolutely. When we do the stem cell transplant itself, we actually do prophylaxis for graft versus host disease. Almost all patients will be on steroids, some form of immune prophylaxis. It may be tacrolimus. It may be sirolimus. There are some newer drugs. And in spite of that, if we see graft versus host disease, we have some very good medications.

In fact, some recent drugs approved such as Ruxolitinib, Ibrutinib, etc., which can work. But in spite of all of that, I would say a majority of patients do face a struggle with graft versus host disease. And they do have some degree. Now, again, it may not be severe. It may be in the form of graft versus host disease of the mouth, which causes your ability to eat to be decreased, or it may be the skin, which may be itchy or uncomfortable, or it could be ocular, which causes eye irritation and burning and requires eye drops. So, they may not be severe, but they hugely do cause discomfort of that quality of life.

But yes, we do try our best to avoid it. And in some patients, we are able to get away with none. And in some patients, they will have mild to moderate, which has to be treated. Luckily, with the newer generation of immune prophylaxis monitoring treatment, we have very few severe graft versus host disease, which is a good thing.

Beth:

Great. I’m so glad you touched on that. So, I wanted to shift gears a little bit, Dr. Daver, and find out from you what are some of the key takeaways for AML patients and care partners from ASH.

And I also wanted to say what I’ve heard a lot, in regard to AML is that, for almost 40 years, there was just a standard way of treating. And all of a sudden, in the very recent years or maybe year, I’m hearing that there’s so much now, new drugs and things happening. So, would you mind touching upon some of those key takeaways?

Dr. Daver:

Absolutely. I think, this year 2018 was clearly the year of AML. There’s just, compared to all of the other malignancies, in the last two years, there’s just been a huge amount of progress in the way of approvals. Now, what I do have to say is, although we are seeing the fruits of a lot of efforts, actually, the research in AML has been very intensive for the last 15 to 20 years. And what we’re now seeing is really the combination of a lot of those efforts. Molecular, immune analysis, which have led to these drug approvals.

But today, really, I think, compared to even three years ago, when we did not have a number of these drugs, the whole outlook for treatment of AML has changed dramatically. So, we’ve had eight new drugs approved in a few years. And, to put it in perspective, for the 40 years before that, we actually really had almost no drug approved. There was one drug, Gemtuzumab, approved, but it was actually withdrawn from the market. So, when they say when it rains, it pours, that kind of really did happen, in the case of acute myeloid leukemia. But what’s really important, I think, I that there are now a number of targeted therapies towards particular mutations.

And some of these have actually been approved, in the frontline setting. So, now, it has become very important that we don’t just treat all AMLs as one disease. In fact, that’s something we knew for about 20 years that AML is one of the most heterogenous of all malignancies. Lung cancer and AML, these are probably the two most heterogenous cancers where it’s not really this is AML, it’s different types of AML, which can have prognosis of 95% cure rate all the way down to 10 to 15%.

So, identifying these groups was very important for prognosis. And that’s something we have been doing but more important for treatment. So, for example, a mutation that is called an FLT3 mutation is very, very important because, on its own, it is associated with an adverse prognosis. These patients had high white counts, proliferative disease, and their three year or five-year survival was usually 20 to 25%, when we first identified this mutation in 2001. Now, there are new drugs called FLT3 inhibitors that specifically inhibit the FLT3 mutation pathway.

And with the addition of FLT3 inhibitors, specifically a drug called Midostaurin that was FDA approved 1.5 years ago, plus stem cell transplant, and even more so, at the recent ASH 2018 meeting doing post stem cell transplant, FLT3 inhibitor, when we do all of these three interventions, we’re now getting up to five year plus survival rates of 75%. So, this is amazing.

The patient who was 25% 12 years or 13 years ago, when we first identified this mutation, could today, if appropriately treated with FLT3 inhibitor transplant and FLT3 inhibitor maintenance, could be in a 75% long term survivor rate. So, tripling those outcomes. And similar things are being seen for other groups. For example, APL, acute promyelocytic leukemia, is one disease where we actually are able to treat these patients without chemotherapy. So, you can give a combination of ATRA arsenic, which gives you 95% cure rates.

So, the key now, and what I tell a lot of our community doctors, our fellows, other academicians is it’s not about just rushing in treatment, which has been the paradigm for 30 or 40 years, but more important, it identifies specific molecular mutations or cytogenetic changes and choose the best treatment because the impact of choosing the appropriate molecular or non-chemotherapy or antibody based treatment is, actually, much more than quick therapy. And I think that message now is going out.

And things are improving overall.

Beth:

Wow. And what I’m hearing are two things. Eight new drugs, however, those eight drugs are specifically going to be used, in regards to different mutations. And so, my question to you is it’s very obvious that genetic testing, for these mutations, is a huge puzzle piece to this. And could you talk a little bit about that. At what point can a patient get this genetic testing from the mutations. And if you could just speak to that because it just sounds that is essential?

Dr. Daver:

Yeah, absolutely. I think that is probably the No. 1 takeaway for both patients, caregivers, and physicians. So, the genetic testing should be done for all new AMLs at the time of diagnosis. And there are a number of different labs across the country, commercial labs, that are able to do this new genomics, foundations, hematologic, all of these are not insurance approved and covered.

Some of the larger academic centers have their own molecular testing analysis. The most important thing is that we should usually wait for these results before rushing into therapy. And just to give an example, when we see a new AML at MD Anderson, we will rush their cytogenetics and molecular testing. We’re looking for cytogenetics to rule in or rule out APL, acute promyelocytic leukemia because this can be treated without chemotherapy with 95% cure rates. The other big group we’re looking at is what we call core binding factor leukemia. These are a group of specific chromosomes associated leukemias.

And if you find those, then, that is the group or the addition of the antibody treatment called Gemtuzumab Ozogamicin or Mylotarg, which is FDA approved, can improve the survival rates by almost 20%, which is a huge amount on top of chemo. So, you don’t want to miss identifying this core binding factor of chromosomes. Then, if we don’t find one of these two, then, we rush our molecular panel.

We are fortunate. We get the molecular results in 48 hours. That’s one of the places in the country. There are a few other groups that are in the same range. But even in the commercial setting, I know for a fact that they’re able to get these results in six to seven days. So, I think it is actually possible and feasible. And even on some of the large trials we’ve done across 100 plus centers, we were able to safely wait for those results. Two molecular results were most important looking for our FLT3, if you find that mutation. We want to add the FLT3 inhibitor up front, and then, IDH1, IDH2 mutation.

And if you find those, we may consider, on a trial basis, adding IDH1, IDH2 mutations. And then, if none of those mutations or chromosome groups are identified, then, we will consider standard treatment. But even there, we have trials where we’re adding new drugs, which have shown very high activity like Venetoclax or Nivolumab or immune therapies to standard chemo. So, really, this is now personalized therapy. There are five clear subsets of AML that will have different treatment approaches.

And addition of the appropriate agent could improve your survival and cure rates from anywhere from 10 to 30 or 40%. So, I think this is quite important.

Beth:

It’s just amazing. And what I’m also picking up on, and what I’ve been told about AML, is that you need to move quick. This is, once diagnosed, time is of the essence, and especially with the different subtypes. So, we’re talking about genetic testing. And I really, really was very interested in hearing how it works and how quick it could be turned around. But what would you say – we very often hear, like in Steve’s case, it was his doctor who referred him to a local hematologist and then, eventually, to a specialist? Sometimes, we hear people being rushed to the hospital or going to their local doctor. But time is of the essence, in getting this genetic testing.

What advice do you give patients who, typically, might go to a local doctor, how to move along in this process and how to advocate for that genetic testing? Do you have any feedback on that?

Dr. Daver:

Yeah. I think there’s a fine balance. And that’s where it’s hard to make a generalized recommendation across the board because there are some AML patients who come to us who have a very high white count, more than 100,000, for example. They may have evidence of leukemia already infiltrating their liver or kidney, with organ abnormalities and lab changes. And in those patients, we may have to start treatment very early. But those are the minority. We’ve published, as other groups have looked at this, those make up about 5 to 10%. So, in the majority, it is, actually, a mindset change.

And this is something we’re doing a lot of education on, as well, is that that mindset of the sun should never set on AML. We have to treat right away, actually, was true, when you didn’t have other effective therapies that could be added that could change your outcome from 25% to 75%.

But today, in fact, I think it’s much more important to select the appropriate treatment or the addition of the appropriate molecular immune therapy than rushing into treatment. In fact, our group, as well as a number of other groups in the country, have published it. So, what we recommend, in general, is we get a new AML. We would admit those patients. I still think this is an inpatient disease. We would monitor them closely. We send, on the same day that we see them, a molecular chromosome panel. We ask it to be rushed. And then, usually, we can get these results in three to five days.

And I would wait to get those results because, based on those results, we may choose a FLT3 inhibitor. We may choose the antibody Gemtuzumab. We may choose IDH therapy. We may choose ATRA arsenic. So, I think, for most patients, what you could do, of course, you have to be careful when you’re discussing it with a physician, you don’t want to push on them too much. But I think it’s important to ask about molecular therapies, molecular trials, whether we could get the molecular information early, and how we could incorporate that.

I think, the good thing is we’re seeing, across the country, most of the physicians are taking this approach. And there is very intense education. But I still think it doesn’t hurt to ask about it and make sure that that testing is being done because I think it could make a huge difference in your outcome.

Beth:

Great. Wonderful feedback. Now, Leah Szumita, I’d like to bring you in on this conversation because we heard eight new medicines right now. That’s huge. And as Dr. Daver said, those are the results of clinical trials. And, recently, I heard that only about five to eight percent of adult cancer patients are participating nationwide, in the United States, in clinical trials. That seems like such a small number. And we depend on these patients to participate in these clinical trials to come out with these eight new meds.

There’s definitely a gap. And I’d like to hear your feedback about just that. And then, if you can go into – I’m going to ask you a few more questions about how people get involved in clinical trials. So, take us through that.

Leah:

Great, I will. So, I have to echo Dr. Daver’s sentiments about the importance of the genomic testing as well. And really, the new breakthrough in AML therapy is just a testament to the ongoing research. As he said, the research has been happening for 15 or 20 years. And we’re finally seeing the fruits of the labor. So, it’s encouraging. And that five to eight percent is low, but there’s room for improvement. And I think many different organizations have identified barriers to why these enrollment rates are so low. I will say that, of all of the clinical trials, somewhere between two and ten percent of clinical trials have to close because of low accrual rate.

So, there is just serious work to be done. I think, you can look at barriers in two different ways. There are patient barriers. There’s just a lack of awareness that clinical trials exist for all stages of diseases. So, many people believe that a clinical trial is only for those who have exhausted all other treatment options. And so, that’s actually not true. There are trials for every stage of disease. Previously untreated, newly diagnosed, relapse refractory, maintenance and remission. There are other barriers that people are afraid to be a guinea pig.

And so, I think, as healthcare providers, that’s our job to really educate that clinical trials are very controlled, closely monitored situations, provide education on the different phases and what those mean. There are very complex and stringent inclusion/exclusion criteria to clinical trials, which, in one way, can make it very difficult to understand, if you’re even eligible for a trial.

And so, that’s why clinical trial nurse navigators, such as myself, can really help patients and caregivers sort through that information. And then, sometimes, physicians aren’t aware of all of the trials that are out there either. And that is not to slight practitioners, but, again, it’s just an overwhelming amount of information. It takes time to stay on top of all of this research. It takes time to go through all of this research and all of the different protocols.

And so, it’s really important for patients and caregivers to have an advocate to try to identify what clinical trial is right for them.

Beth:

And so, through the Leukemia and Lymphoma Society, you offer this service, if I understand you correctly. So, patients and their caregivers can reach out to your department and find out what is there for me. What comes to mind, also, I hear quite often, and we’ll get Dr. Daver’s opinion on this as well, in just a moment, but there seems to be roadblocks to people, not only I don’t want to be a guinea pig and understanding that piece of it, but also are there some financial hurdles, geographic hurdles?

I hear from patients, quite often, that I live so remotely. I’m in a rural area. How would I manage this? So, could you give a little feedback about that?

Leah:

Sure. First, with regards to the financial barriers, another common myth is that a clinical trial is free. And, unfortunately, it’s not. I would say that, often times, whatever is being studied, either a new drug or a combination of drugs that usually is covered by the sponsor of the trial. But the rest of the care needs to be billed to insurance. And then, there’s this third bucket of cost, which is the money it takes to get someone and their family members to and from all of these appointments, prolonged hospital stays away from home. So, those are significant financial barriers to participate, in a clinical trial.

There are resources out there to help navigate through some of these obstacles. And, again, I would encourage people to contact Leukemia and Lymphoma Society. We can help steer you to those resources. With regards to the geographic barrier, it’s correct. A lot of these large, academic medical centers are not in proximity to people in rural areas. And that is one key point of clinical trials that needs to be improved upon. And I think a great goal would be to get some of these later stage, later phase trials out into the community setting where they may not require quite as intensive monitoring.

But it can also be available to more patients and really diversify the patient populations.

Beth:

Great. Really great feedback. And then, Dr. Daver, I know that your center is very proactive with communicating clinical trials to patients. And could you just speak about that a little bit?

I know it must be overwhelming. You’re doing your research. You’re a clinician working with your patients and to keep on top of every clinical trial. But, again, I know that that’s something you’re very, very on top of. But could you give a little feedback about how you approach that?

Dr. Daver:

Yeah. As an AML expert, I would still say I’m not really aware of every AML trial, in the country. It’s not possible. There’s 200 or 300. And they keep changing every week. So, nobody really, at a clinician level, is going to be completely aware. Now, what we do know is the comorbid areas, the targeted groups, the particular mutational groups of trial, the new trials, and, of course, what’s looking more exciting, whether it’s in Phase 1, Phase 2, or Phase 3 development. I completely echo the sentiments. I think 100% of our efforts should be to get patients on trial. And, at MD Anderson, we have 180 trials in leukemia alone of which about 70 or 80 are in AML.

And, of course, this is on the higher end of the spectrum. But the focus is really to enroll people on trial. And, I think, what patients often, and I hear this almost every day in clinic, is that they’re concerned because, when you say a trial, they are thinking experimentation. I think there’s a big difference in experimentation and clinical investigation. So, our effort is always to offer trials that give you standard of therapy plus something. And, in fact, whenever we’re treating a frontline patient, no leukemia expert, least of all, in a very large academic center, is going to randomize the patient to something other than standard of care.

But what we do want to see is can we improve the standard of care. And that’s how all of these new drugs go approved. So, we were doing these trials with FLT3 inhibitors added to chemotherapy for almost 10 or 11 years at some of the large centers in the country. Similarly, with IDH inhibitors or Gemtuzumab. And I have many patients who, seven, eight, nine years ago, were able to go on these trials, many, many years before the FLT3 inhibitors approved and get those benefits.

So, the way we like to put it is to try to get you tomorrow’s therapy today. So, you’re going to get access, approximately, four to five years before a drug is approved. And almost always, you will get the standard treatment plus something. So, you’re not going to get less. You’re going to get more. Now, of course, all of the additions may not work. But the chance is that at least you’ll get the benefit of standard agent plus something. And a lot of times, when we explain that, then, patients, of course, say I would like the trial rather than just standard of care.

The other thing is, with the cost, although it’s true that the drugs may not all be free, at least you may get some or part of, in some cases, all of the drugs free. So, at least there is some incentive there because, a lot of times, people say the insurance covers it. But the cost of a lot of drugs is astronomical. And even if you’re paying just 5% for an average AML drug targeted therapy, which is somewhere between $15,000.00 to $20,000.00, that 5% can be $1,000.00 to $1,500.00 a month.

So, a lot of times, what I see from my patients is, when they go on our trial for FLT3 inhibitors and IDH inhibitors, and even the fact that they’re not paying their co-pay, often offsets their cost of coming to MD Anderson or coming to Dana Farber or Sloan Kettering or whatever it may be. So, I really think that one should definitely talk to the Leukemia and Lymphoma Society, other major organizations, so that they can find out what trials are there. And many times, patients say, well, don’t think there’s a trial for me, or their local physician may not be aware.

And I can guarantee you, almost 99 to 100% of the time, there will be not just one but many, many trials that are available to you. So, I think that little bit of effort, emails, phone calls can go a long way.

Beth:

Great feedback. And Leah, going back to you, excuse me – I’m sorry. I just need to stand up a moment. I’m in a room that decided the lights would go off. But you can all hear me. Speaking to you, and I’m getting towards our lights, can you talk about what questions someone can ask their doctor, in regard to clinical trials?

What are those important questions?

Leah:

Absolutely. So, there are so many of them. And one of the things that my group of nurses and myself do is really provide people with education about the basics of clinical trials and then, the language and the questions they can use, when they go back to their provider. And then, also, when they go to make that connection with the clinical trial group. So, the list is long. I would say first and foremost, asking what the risks and benefits are. Many times, in a clinical trial, there are different requirements about how often someone might come to and from the site, what the finances might be related to that.

Also, a lot of studies or drugs used in studies have been used in other studies. So, asking if there are any early results or any results from prior studies using those medications is important.

And asking about how this may affect quality of life, all of those different kinds of questions. There’s a very long list. We do have a fabulous clinical trials booklet that patients and caregivers can obtain that have lists of questions. And we always encourage people to read through that material as well. But knowledge is power. So, the more knowledge and research someone does, and bringing someone with them to these appointments to really take notes because it can be so difficult to absorb all of this information, would be some of my recommendations.

Beth:

Wonderful. Great feedback. So, Steve, I’d like to circle back to you now. You have this overwhelming, very intense journey. Where did you get information about AML? Where did you get support? We hear that so often, when someone is diagnosed, and they have to handle and make decisions fast, what kind of resources did you utilize. And tell our viewers out there, so the can understand what to do and how to do it.

Steve:

Well, one thing I did not do is go on the internet and scare myself half to death. I trusted my doctors. It did happen so quickly that I was in treatment before I even understood the nature of my disease. So, for better or worse, I was getting on that train and going wherever it was going to take me. But I had a great team of social workers. I had great nurses. My oncologist was excellent in spending as much time with me as I wanted. And so, it was a gradual kind of learning curve for me. And the fact that the early treatment went pretty well, obviously, helped give me confidence.

And the same thing, when I went down to the University of Minnesota Medical Center. They gave me a very thorough explanation of what was going on, recommended the stem cell transplant. I had a colleague whose father actually worked in this area decades ago.

And I talked with him. He stressed the importance of getting a second opinion. So, I was able to go to the Mayo Clinic, which is about an hour and a half drive from where I live. And I talked, first, to a hematologist who said I can tell you some things, but you should come back and talk to the transplant experts here. So, I did that as well. So, between my initial oncologist, my transplant oncologist, my second opinions at the Mayo Clinic, I was pretty confident that not that it would all work out, but this was the best path to follow. And as I followed that path, I did get invited to a clinical trial.

Just from a patient’s perspective, some years ago, I was the caregiver for my mother, as she was struggling and eventually dying of breast cancer. And her oncologist wanted to put her in a clinical trial. And I was very suspicious, and wondering is she not going to get the kind of care that she needs because you want to use her as a subject in a study. And I declined that study. And some years later, I find myself being invited to join a study. And I asked a lot of questions, especially when I saw that 22-page consent form.

That’s pretty daunting. There’s a lot there, and there’s a lot to ask about, and I did. And people patiently answered my questions. And I just came to realize, essentially, in my case, the trial wasn’t even close to experimental. What they were saying is this is how we’re going to treat you regardless. But if you’re willing to do the study, we’re going to track the results. And that can help people down the line. So, at that point, it seemed almost like a no brainer. And I could have chosen my brother as a donor or a stem cell as a donor. Instead, I went into a study that randomized me. And I went into the stem cell, and it turned out just fine.

But they said the five-year survival rates for either path are about the same, so that’s why we’re doing the study to try to figure out what the different pathways are to that outcome and when something will benefit patients in the future. So, at that point, it just seemed like a reasonable thing to do. Helping people understand that you’re going to get the best treatment they can give you regardless, even though you’re in the study. I think that’s, for many patients, the key point. And it sounds like Leah and her folks are working on that angle.

That’s really important for patients.

Beth:

Wow, that is fabulous feedback. And if you could say – what I’m hearing you say is that you got a lot of support from, it sounds like, the hospital where you received your care. That there was you mentioned social worker, and they sounded like they were really there to give you support. Would you agree that everyone really worked together to help you through this journey?

Steve:

They did, both the professionals and circle of friends and colleagues. Of course, those email correspondences, as I said, I was getting multiple responses to every email that I sent out, from various people. Sometimes funny, sometimes dark humor, which I especially appreciate. Thank you, Dave, from Milwaukee. So, a variety of things that came in, people prayed for me. I’m not especially religious, but whatever they wanted to do was fine with me. So, the writing, again, was therapeutic.

I practiced a lot of mindfulness and meditation and yoga. I was a very active patient. I walked the halls five miles a day. When I couldn’t leave my room, I was on a treadmill. I just needed to do things that sort of kept my body up and moving. And I think that really helped my recovery. I had nurses tell me, at one point, I was doing better than any other patient, at that stage in treatment. I’m not bragging about it, but I think, again, initial good reactions made it easy to get in this upward spiral. I exercised, I ate as well as I could. And I’ve seen patients have a bad time. And they’re kind of in a downward spiral.

And it’s really hard to reverse that. If you don’t feel good enough to teat, if you don’t feel good enough to exercise, it’s really hard to get out of that box. And so, anything you can do or anything nurses or social workers can do to help patients be proactive, be as active as possible, ask lots of questions, in whatever fashion suits their needs. Try and tell your story, whether it’s Caring Bridge, or emails, or verbal recording of what’s going on, I think there’s a great therapy to just trying to put together, from a patient’s perspective, what the hell is going on here and what’s happening to me and how might it turn out.

And those are some of the things that helped me get through.

Beth:

That is just great feedback. And Dr. Daver, I’m picking up that Steve has just an amazing attitude. And what kind of feedback do you give about that? These patients, these wonderful people, their lives have been turned upside down. As you tell us, it’s just very quickly, they’re living one life and now another. How much do you see, listening to Steve’s attitude and trying to be proactive and advocate for himself, do you feel that’s an impact on overall success in treatment and moving forward?

Dr. Daver:

Yes, absolutely. I think that the attitude plays a major role. But I think a few things that Steve said are very important.

One is that he did seek out second opinions. He did go to Mayo Clinic, a very large academic center. He got additional input. He learned about clinical trials and outcomes. And a lot of times, we have patients who may contact us or physicians from outside who contact us or come to us. And sometimes, we may not have something different to offer. There may be a standard treatment. A lot of times, the peace of mind of knowing that you have consulted with a large academic center, one of the top centers, whether it’s Mayo or MD Anderson or Sloan Kettering, whichever it may be, often helps a lot.

And then, there may be other times when we actually do say, and this happens quite frequently, that, actually, we have a trial that I think will be a better FLT3 inhibitor or better IDH inhibitor or a better antibody. And this is what I would do, if I was in your place, or if I had a relative in your place. So, I think that helps your peace of mind and your mental framework. And the second thing is – and that’s not something we can control is how you do to the initial treatment.

If you have good responses, if you tolerate it well, then, of course, we do see that those patients are always more optimistic, have a better mental framework, it helps. But I also see that there are some patients who come in, with a very negative framework. And that’s where I think learning that there is so much new progress, that there are so many options, not only in the frontline setting, in the relapse setting, in the maintenance setting, even after post-transplant relapse. We have things that, potentially, could cure patients, which we didn’t have even five years ago.

So, I think knowing that there’s a huge amount of progress, that the cure rates have doubled, tripled, in some cases, in elderly AML and FLT3 AML. And no longer having AML is the end of the world. In fact, in our most recent data update that we are going to publish soon, we see that, in the young patient, 65 and below, the overall survival, if you gave all patients who visited MD Anderson is about 66%. So, 23 patients actually had a long-term cure.

And people are shocked, even physicians I know of in the ICU and ER settings, don’t realize this fact. In elderly AML, it’s tougher, but we are going from 10% to almost 45 or 50% cure rates in patients 65 plus. So, I think, once people hear these numbers, they completely change their mind and are much more optimistic. But getting that information across to patients, to caregivers, to make them do the referral or make them consider treatment, I think, is the first big hurdle that we have to kind of overcome.

Beth:

Wow. And that is just very right on target. So, I’d like to shift gears a little bit. We do have a few questions we have time for. And Dr. Daver, the first question I’d like to get your feedback on, and forgive me with the pronunciation of the actual medication, I’ll try my best. So, this question comes in, what is the role of Venetoclax, if any, in treating AML. And when might that be FDA approved, from what you might know about this?

Dr. Daver:

So, the Venetoclax is probably one of the most exciting drugs in AML, especially elderly AML. In elderly AML, it is the most exciting drug that we have had probably forever. So, we used to treat elderly AML, meaning above 65 years of age. And these are hugely people not just by age, but also based on the physician’s review who are considered not fit for intensive chemo. They may have kidney problems, liver disease, poor performance status, immobility. And so, we cannot give the high chemo, the 3 + 7 that Steve got. And we have to use lower intensity therapy.

And we used to use Azacytidine alone, with the response rate of about 20 to 25%- and 3-year survival of about 15 to 20%. And now, we’ve done a study using Azacytidine in combination with Venetoclax where the response rates were 73%. So, going from 25% to 73% not doubling or really tripling, and that the survival is now 46 or 48% going from 15 to 18%.

So, that’s a huge, dramatic shift, three times response rate, three times of the potential cure rates. So, I think, right now, we believe that Azacytidine and Venetoclax really should be the standard of care for elderly AML, if they’re not going to get induction chemo. And, in fact, it was FDA approved very recently. So, three weeks ago, in fact, right before the ASH meeting, end of November, Azacytidine in combination with Venetoclax, as well as low dose Cytarabine and combination with Venetoclax were FDA approved.

And I think, now, with the approval, although we were doing this even before the approval, no elderly AML patient should get Azacytidine or low dose Cytarabine alone. I really think addition of Venetoclax now is the standard of care, triple response rate, triple survival. There’s no reason not to do that.

Beth:

Wow. That is an amazing shift and such good news for our elderly patients. That is great. I do have another question. And I believe it’s targeted for you as well, Dr. Daver.

For those young folks, under 35, who relapse quickly, within about 100 days after MUD allo transplant for AML, M5, no mutation target, what will be a sustainable way to buy time and bridge for that next transplant. Could you talk a little bit about that?

Dr. Daver:

So, that’s a very tough scenario. Relapsing post-transplant itself is a very high-risk feature. It, basically, indicates that disease is aggressive and may not respond to further chemotherapy or transplant. But relapsing early post-transplant, which we usually consider within 100 or 120 days is actually quite an adverse feature. So, for those patients, I think the best chance is if we can find a targetable mutation. So, we will be looking for FLT3 or IDH1, IDH2 mutations. If we find those, then, I think we do have some chance with either a FLT3 inhibitor alone or, more likely, in a FLT3 inhibitor, in combination with low intensity therapy.

And there are a number of these agents either approved, but I would actually go for a trial where we’re combining either FLT3 inhibitors or IDH1, IDH2 inhibitors with other exciting agents like Azacytidine and Venetoclax. I think that will be the best shot of getting a long-term remission, potentially, a second transplant. Of course, there are a lot of caveats and variables. And you have to look at the individual patient to make that determination. The other group of therapies that you could use, if we don’t find the FLT3 or IDH because only about 30 to 40% of patients will have one of these three mutations, is immunotherapies.

And these can work really well, especially in the post-transplant relapse setting. And we have drugs such as antibody drug conjugates. These are antibodies that carry a toxin and can attack the leukemia cells. Or what we call immune check point antibodies. They’re also agents that activate your own immune system post-transplant to fight against tumor. And with these, we have seen some very exciting activity, specifically, in the post-transplant relapse.

And a lot of these are all under clinical trial setting because the antibodies and the immune checkpoints are not yet approved. They may be in the next couple of years. So, I think this would be an ideal scenario to find the academic center close to you and try to consider getting into one of the trials, either targeted therapy or immune therapy.

Beth:

And another question would be do you see post-transplant relapse more in specific mutations? Are those with specific subtypes of AML?

Dr. Daver:

Yes, we do. So, we see the post-transplant relapse most common in what we consider the adverse risk AML. So, the adverse risk AML are the patients we definitely take to transplant. But, unfortunately, even after transplant, they remain the group that have a high risk of relapse. So, these are patients who have what we call TP53, one of the worse mutations. They will often have a high risk of relapse post-transplant or chromosome changes like deletion 7, deletion 5, deletion 17, also another high-risk group.

And the third group is what we call secondary AML. So, there are two ways you could get AML. You could have spontaneous AML, most common. We have a patient, no prior history of chemo radiation, other cancers, who comes in with acute diagnosis of AML. But then, there’s another group making about 20 to 30% called secondary AML. So, these are people who have prior breast cancer, colon cancer, bladder cancer, and got either chemotherapy or radiation for that. Or people who had prior MDS, which is an AML precursor and then, developed AML.

And these people who have secondary AML are much more risky and also more prone to relapse post-transplant. There are a few new drugs like Vyxeos that can work well, in this situation. But, in general, these are probably the high risk molecular or morphological groups that could relapse post-transplant.

Beth:

Very interesting. Well, I so appreciate all of the wonderful information and feedback that our guests have provided today.

And the timing is great. Just coming off of ASH has been extremely encouraging, Dr. Daver, with you sharing all of these wonderful new eight new drugs and insight that’s going on. And, Leah, your feedback has just been phenomenal. And really, I believe it’s going to ease people’s concerns and fears about clinical trials, and between you and Dr. Daver speaking about the clinical trials, why they’re so essential, and they’re doable. And, Steve, your feedback, not only about clinical trials, but your journey is phenomenal. And I hope our viewers look forward to seeing information.

We may not have mentioned this. Steve has written a book soon to be published about his journey. He has some very interesting feedback that we just didn’t have enough time to share on today’s webinar.

So, thank you, again, to our guests and our sponsors. And a replay will be completed soon. And you’ll receive it via your email. So, our audience, please look forward to that. And remember, be your own advocate. Thank you.


We thank Celgene Corporation, Daiichi Sankyo, Genentech, Helsinn, and Novartis for their support.

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.

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.

Clinical Trial MythBusters: Actionable Advice for Knocking Down Obstacles to Trial Participation

Actionable Advice for Knocking Down Obstacles to Trial Participation

Downloadable Program Guide

Clinical trials offer tomorrow’s medicine today, but more often than not, only a small fraction of patients ultimately enroll in a trial due to barriers posed by financial logistics, distrust and travel, to name a few. In this MythBusters program, we will examine the barriers to enrollment, evaluate patient needs and discuss resources to help guide people through the clinical trial process with the help from two experts, Dana Dornsife of Lazarex Foundation and Myeloma Survivor Reina Weiner.


Transcript:

Andrew: Hello from Carlsbad, California, near San Diego. I’m Andrew Schorr from Patient Power. Welcome to today’s Patient Empowerment Network program, clinical trials myth busters and actionable advice, resources for knocking down obstacles to trial participation. I wanna thank the companies that have provided financial support for this program. They have no editorial control, but we definitely thank them for their support. Those supporters are AbbVie Incorporated, Astellas, Celgene Corporation, and Novartis.

Okay. We have a lot to talk about. First of all, I’ll just say I’ve been in two clinical trials; one Phase 2 many years ago at MD Anderson for the leukemia I have, chronic lymphocytic leukemia. And that gave me tomorrow’s medicine today. It worked, but I had travel far to do it and there were costs involved.

And then I was in a second Phase 3 trial close to home, and that was good too, and discovered another cancer that I have, myelofibrosis, through the monitoring in the trial. So, I’m a believer, but there are obstacles, and let’s talk about some of these. And we’re gonna give you some very specific resources to overcome these obstacles, so that hopefully, if a clinical trial is right for you, you can participate, you can feel good about it, and you can move medical science along to help everyone who is dealing with that condition.

So, what are some of the issues? Financial, of course; logistical issues, of course; distrust, are they really gonna take care of you or are they gonna protect your safety? Is it really right? And are you being given the straight scoop? What about travel costs? I went from Seattle to Houston, Texas a few times. Costly, okay? Stay in a hotel. It’s costly. Get a babysitter, leave work; costly.

The guinea pig syndrome; you’ve heard about it so many times. Are they gonna experiment on you, and are they really protecting you, and are you a number, or you are a person with cancer, or your loved one? And then is your medical team that you’re talking to about your treatment, are they informed about clinical trials? Or are they pooh-poohing clinical trials because they don’t wanna do the paperwork, or it’s happening down the road and not at their clinic. Lots of issues; we’ll talk about that.

Okay, I got some great helpers. So, first let’s go to Asheville, North Carolina, and you are used to live in Charlotte. Reina Weiner joins us. Reina, welcome to our program today. There we go. Say that again, Reina, you were muted.

Reina: Thank you.

Andrew: Okay. Now we should tell you that last June, well, June of 2017, Reina had a autologous transplant for multiple myeloma. And along the way, leading up to that, over many years she was in four trials. So, first of all, Reina, let’s start with what’s most important. Post-transplant, how are you feeling today?

Reina: I’m feeling very well. Thank you, Andrew.

Andrew: Okay, and what’s coming up at the beginning of September?

Reina: What is coming up at the – oh, a big party is coming up. Our children are throwing us our 50th wedding anniversary party, so that’s been cool.

Andrew: Yeah. Well, congratulations. And you’ve been dealing with what became multiple myeloma since 1999. We’re gonna come back and track that in a minute, as far as the steps along the way, the concerns you had or not at different times about being in four clinical trials.

And now let’s go up near San Francisco in the East Bay of San Francisco Bay, Danville, California. Dana Dornsife. And Dana is the Chairman of the Lazarex Cancer Foundation. Dana, thank you so much for being with us.

Dana: Thank you, Andrew.

Andrew: Okay. Now ladies and gentlemen, I want you to know Dana and her husband and her family, overall, they’re incredibly philanthropic across a number of issues that are faced globally, and also in the US. But one of them is helping people with the financial issues that prevent them from being a clinical trial. So, Dana, this is a personal story for you, so maybe you could just tell us why did you start the foundation? It was a family issue.

Dana: It was a family issue, and that family issue really revealed to me a gap that exists in cancer care for advanced-stage patients who want to remain in their battle with cancer through clinical trial participation. My youngest sister’s husband, Mike, was diagnosed with pancreatic cancer in his early 40s. He was given one half of one percent chance to live, and at the time 35,000 people a year were diagnosed, and 35,000 people a year were dying from pancreatic cancer.

So, we decided as a family that if Mike wanted different results that we would need to do something different. And Mike and Erin went ahead and pursued standard of care, and I was tasked with identifying clinical trial opportunities for Mike. And, of course, that sounds very linear, but in fact, for a layperson it was a very difficult task to undertake. I did identify some trial opportunities for Mike. He did participate in a trial and responded well for a period of time, he had good quality of life.

And during that period of time he was meeting people who were asking him, “Hey, what are you doing? I wanna do what you’re doing.” And he would say to them, “Oh, just call my sister-in-law, Dana. She’ll help you.” And that’s literally how this organization began. Through those phone calls that I was receiving from other pancreatic cancer patients, I began to understand that Mike was able to take advantage of medical breakthroughs in clinical trials because he had a family who could afford to support him through the process. And all of these other families that I was talking to, they just didn’t have the financial wherewithal.

So, we started Lazarex in order to fill that gap and help people identify clinical trial opportunities, and then provide financial assistance to them to help cover the out-of-pocket expenses that create huge barriers for patients who are already experiencing financial toxicity due to their disease.

Andrew: Well, thank you for what you do. And we’re gonna talk a lot along the way about resources. There’s a downloadable guide that you’ll be provided with, along with a link to the replay of this program. And that’s gonna have specific resources that you can access, whether it’s financial issues, other issues you may be facing. So, look for that.

Today we’re really focused on actionable resources. So, let’s go to Reina for second. So, Reina, you had been in the pharmaceutical industry.

Reina: Yes, I had.

Andrew: So, you knew about drug development, and you understood about clinical trials. So, I’m willing to bet you were pretty proactive. People who weren’t in the field, they don’t know from clinical trials, and maybe they’d been worried about it. They’ve worried would they be experimented on, would they be a number and not name, would they get quality care. But you were probably, I have a feeling, pretty proactive. And you write about that. I know you have a book as well. So, is that Step 1 for people to speak up for themselves?

Reina: It is Step 1; absolutely, Step 1. And what I found is, first of all, people don’t know about trials. And if you go to a small community practice where they’re very busy, they don’t have the time, they don’t have the staff to really educate patients about trials, the best, best step for patients to take is to ask, “Is there a clinical trial that might be appropriate for me?” That’s huge.

Even when I went to a very well respected hospital and there was a researcher who was following me as I had smoldering myeloma and the numbers kept going up and up and up. I said is there – because I was living close to the NCI – is there a trial that would be appropriate to me at the NCI. And he said just a minute, turned around, went to his computer, found the trial and that’s how I got in.

Andrew: But it wasn’t at where you were receiving care or being monitored at that time. It was somewhere else.

Reina: It was not. It was at somewhere else.

Andrew: Okay. Dana, is one of the obstacles, not just financial, or maybe it’s even the business of cancer where if an oncology practice that you’re going to that’s maybe close to home is not doing the trial, maybe it’s not even in their financial interests to tell you. I mean, is there an awareness issue, do you feel?

Dana: There’s a huge awareness issue there, Andrew. And it all starts with knowledge is power, right, so I completely agreement with Reina’s comment about one of the first questions you need to ask is, is there a clinical trial out there for me because many doctors who are in community environments don’t offer that information. It’s not what they do every day. They’re there to administer standard of care. Only 6 percent of doctors actually engage in conversation with their patients about clinical trials, and that’s usually the 6 percent who are associated with research universities, right?

So, knowledge is power. If the patient doesn’t know about a clinical trial, they’re never going to participate. But once you find out and once you’ve identified an opportunity, the second biggest hurdle is that out-of-pocket expenses associated because most patients have been dealing with their disease for a longer period of time, and they’re basically broken in every way: physically, emotionally, spiritually, and, sadly, financially.

So, patients start to make decisions about the outcome of their care based on the size of their checkbook, and not focused on what’s best for them. And so, Lazarex eliminates that financial barrier as well to help patients say, “Yes, I can participate,” and we can get them where they need to be when they need to be there.

And that’s just the tip of the iceberg, Andrew, because there are many other barriers that exist; socioeconomic barriers, language, culture, historical barriers. And we are tackling all of those barriers one at a time. But really, the biggest two barriers are knowledge and financial.

Andrew: Right. And you mentioned about the historical barriers. Some people know about the Tuskegee experiments with African-American people, so in the African-American community, there still is a distrust among some people. Yet if you think about it from the FDA’s point of view where a company that’s developing a drug, or the NIH, they say okay, how does it work on broader populations or different ethnic groups or different ages or genders, et cetera?

They want to understand that data, and so not just having a number of people participating in the trial, but having it reach people who are in different situations, if you will. And so –

Reina: And if I may – ooh, I’m sorry.

Andrew: Reina, please, go ahead.

Reina: Well, if I may say that because people don’t know about it and the trials, the best trials, are trials with a variety of patients, but they do try to accrue populations who are certain ages, certain genders, ethnic groups, whatever they can get. And only 3 to 5 percent of patients participate, cancer patients, participate in clinical trials, and so much is lost if people don’t participate.

Andrew: Here in San Diego it’s sort of a pocket of a lot of medical research. There’s a lot up in your area, Dana, in the Bay Area, San Francisco Bay Area. I mean, it’s in North Carolina in the research triangle where that’s home state for Reina. And not to disclude others, and then certainly up around Boston. There are like companies all over the place and many of them are in earlier drug developments.

So, when you talk about immuno-oncology now, can we harness our immune system with the help of some medicine to fight the cancer, and I know some people who’ve received it; lung cancer patients who are living, et cetera, melanoma patients who are living for an extended time. These companies can’t move forward unless there’re people who are in the trials. So, the FDA says where’s your data? And they’re saying well, we’re trying, but we haven’t been able to complete this trial. Right, Dana? So, we can’t move towards cures unless we all come together.

Dana: That’s exactly right. So, let me just throw a few statistics out at you that I found astounding when I learned of them. So, we have a 48 percent failure rate of clinical trials, and it’s not because the drug didn’t work. We will never know, quite frankly, if the drug would have worked or not. And we will never know because there weren’t enough patients enrolled in the trials to find out.

So, 11 percent of trials never enroll a single patient, if you can believe that. So, here we are with an almost 50 percent failure rate, and yet we have 600,000 patients a year in this country who are dying from cancer. So, there’s this incredible disconnect between the thousands of patients who would participate in clinical trials if they could, and the thousands of clinical trials that need patients to participate in order to succeed. And without successfully completing those trials, those drugs are never going to get market to help the cancer patients that they are intended to serve and help.

That’s why Lazarex Cancer Foundation exists, and that’s why removing the barriers to clinical trials is so important. Our process does not lend itself well to that. And I just want to take a step back, Andrew, to address the minority participation in clinical trials. We all understand because of epigenetics and, yeah, advances in medical science that we need to have the full spectrum of our population participating in clinical trials. But that doesn’t happen. When you look at the 5 percent of patients who actually participate and you break it down ethnically and racially, less than 5 percent are from minority communities combined.

So, in theory, though we say we understand the importance of that, we’re actually not in practice doing what needs to be done. And so a lot of our work is also focused on reaching out to those socioeconomically challenged and racial and ethnic minority communities to raise awareness and help people like you’re doing on this program dispel the myths around clinical trials, so that they’re more inclined to ask better questions.

Andrew: Right. So, so important, and I applaud for that work. We’re gonna talk about the financial process in a second. Reina, so you were involved in a National Institutes of Health or National Cancer Institute trial.

Reina: Yes.

Andrew: A couple of them, I think, and one at Memorial Sloan Kettering in New York’s premier resources. So, we talked about your tip was you gotta speak up and ask about trials, where they’re at that center, wherever you are, by XYZ oncology in a suburban area, whatever it is or not. So, what’s Step 2? So, for instance, now I understand there are people – and Dana, I’d like your comment on it too.

At some clinics now where there are clinical trial – there are nurse navigators, but often sometimes there are clinical trial navigators too, but often you gotta ask about that too, right, Reina? I mean, it’s speaking up and looking for the resources that are available to you there or wherever you choose to go, right?

Dana: Yes, and there are organizations like Dana’s who help people do clinical trial searches because that’s a bit overwhelming when you are already frightened, you already have the financial issues coming up. And like you mentioned, logistical issues. So, there is Dana’s organization; therefore, myeloma, the SparkCures. There’s the MMRF. There’s the International Myeloma Foundation. There is something called Cis Crypt. And so, they will help you find a trial.

And there are lots of regional trials groups, so you may not need to go to the big, big research center. They might be able to do it locally for you. But I always want to bring up the fact that there’s so much misinformation about trials and what it entails. There’s a tremendous amount of fear. And when I went on the first trial, as I wrote about a little blog recently, everybody said to my husband – well, not everybody, but an awful lot of people said why would you let your wife going in a clinical trial? She’s definitely gonna be a guinea pig.

And I can tell you very, very, very clearly that you get so much care. There’s so much documentation. And the patient’s health is never sacrificed for the research ever. And so, and you sign a consent form, so you’re very clear about what is going to happen. And yes, there’s more there’s more bloodwork. Yes, there are more biopsies. And it’s part of research. And when you sign up, you sign up. And I had more than I’d like to even talk about, but I feel very grateful and very humbled for the care that I received.

And I can tell you, too, that I talked to other people on the trial. And yes, they hope to gain better control of their cancer. But, in addition, they really hope to help the next group of patients who are coming up, so that these new treatments actually happen.

Andrew: I feel the same way. I was in a trial at MD Anderson in 2000, and the three-drug combination I got was not approved till ten years later, but they learned a lot. And you were on a three-drug combination, which I think still has not been approved for first line, but it’s is widely used, I think.

Dana: Right.

Andrew: So, in multiple myeloma. I wanted to mention some other resources, the Leukemia & Lymphoma Society also has a resource center. You can call them. So, there’re these different groups that help you identify a trial, and doctors who specialize, so let’s say pancreatic cancer, you mentioned earlier Dana. I got a call from a friend in Miami, “How do I find a pancreatic cancer specialist?” And I connected them with PanCAN, Pancreatic Cancer Action Network in Los Angeles, who knows who are the doctors who have the most experience with that.

Now, Dana, so then the next thing comes up is alright, I’ve identified the trial, but it’s not where I am. So, now we talk about logistics and finance. So, let’s say somebody calls your foundation. Tell us how it works. So, I don’t have the resources. Maybe they live in Northern California and the trial is in Southern California or in Salt Lake City. What happens next?

Dana: So, Andrew, in some cases it’s not even that distance. In some cases it’s getting from Sacramento to San Francisco, which is literally a one hour, one-and-a-half hours without traffic, in your car. And sometimes it’s a tank of gas, a bridge toll, and parking. I mean, we’re not talking about thousands of dollars in some cases, but it’s still the difference between life and death.

When someone calls Lazarex Cancer Foundation, they can contact us directly. We have a financial application that we use to determine the degree of eligibility for patients to get their out-of-pocket expenses reimbursed. Or they can be referred to us by their social worker at the institution where they are receiving, or thinking about participating in a clinical trial.

We take a look at the household income of the patient, and I believe our guidelines are very generous. We go up to seven times the federal poverty guidelines for patients. And we arrived at that number through trial and error. Our goal is to help as many patients as possible participate in clinical trials, and turn away as few as possible. And then we reimburse on a sliding scale from 100 percent to 75 percent to 50 percent depending upon your household income.

And it’s a pretty easy process to go through in order to be enrolled and receive the reimbursement. And then we reimburse our patients monthly, on a monthly basis. And in some cases, we’ve been working with patients, we follow them, like Reina, through two, three, four clinical trials. And we’ve been supporting them in trials for years. And without doing what we do, they may not be here with us today.

Andrew: Well, I’m sure you’ve saved some lives and lengthened some lives. Reina, so you were in the pharmaceutical industry and in oncology, I believe, before all of this started happening to you. And you’ve continued teaching nurses and devoting yourself to education and your book and your blogs. Thank you for all that. Maybe that’s what life’s about.

But knowing on the inside there are pharmaceutical programs, in some cases, I think, particularly for rare cancers where they may provide assistance. They can’t pay you to be in the trial, but there are at times assistance and travel logistics, particularly for rare cancers where maybe the trial is not, not one hour away. Am I right, Reina? Are you familiar?

Reina: Oh, there are. And sometimes when I was working, there would be a patient who had a cancer that really was not aligned with a particular treatment that would be effective for them. And so, the doctor wanted to try an off-label use of a product, and so then they would come to me and asked me if I could get the pharmaceutical company to provide the drug for free.

And sometimes it takes a little doing, but I was concerned about the patient and hoping to get them a better quality of life, if not an extended period of life. And so, yeah, the company would do that. Not every day, not all the time, but if the company had evidence that this was a patient who would benefit from the off-label use of a product then they would help them out.

Andrew: Okay. So, Dana, related to other organizations providing assistance, and I recently interviewed someone from the Family Reach Foundation where they help with rent or things, groceries, things like that. So, somebody says, “Oh my God, I’m afraid of a trial, I can’t go there,” or if they hear about it and they say, “Hmm, well, maybe I could, but I’d have to leave work, or maybe my spouse would have to leave work, we’d have to find somebody to pick up the kids from school, oh my God.” There are organizations that can help with some of these family processes, aren’t there?

Dana: Absolutely. And I think we’ve provided the Patient Empowerment Network with a list of those. 21st Century C.A.R.E. is an organization that provides patients with immediate financial assistance for expenses related to active cancer treatments. Cancer Care provides assistance for cancer-related costs. There’s a Cancer Care Co-Payment Assistance Foundation. We get that question a lot.

We’ll help with the out-of-pocket travel expenses, and in fact, some of the medical and diagnostic expenses that aren’t covered by insurance. When you’re participating in a trial, sometimes you have to get more stems than insurance will cover or whatever. But co-pays are a big deal for people to be able to afford those, and so, that is another organization that can help. Patient Advocate Foundation, which is an underinsured resource directory.

So, there are a lot of you nonprofits out there who exist to support patients through the fifth process. It’s just a matter of helping patients really understand and put together all of those resources in a way that they can access them.

Andrew: Okay. So, Reina, you’ve been through it four times, and you’re a pretty savvy person. Not all of us know as much, so help us now. So, one of the questions in a trial is, and in cancer, am I gonna get what I describe as the good stuff, knowing that the good stuff that’s being tried may not be good. I mean, it may not work out. There are trials that go bust. Not just for not getting people, but they got people, but it wasn’t as effective as they hoped it would be.

But let’s say we’ve done our homework and we go to a certain clinic, but it’s some sorta controlled trial. We don’t know whether we’ll be in the arm. So, was a concern for you? Were you gonna get the good stuff, and why do it?

Reina: Well, no, really, Andrew, because I know that like if it’s a Phase 3 trial, so you’re comparing standard of care versus the newest and hopefully the latest and greatest. If it turns out that one arm of the trial really shows a significant improvement, patients are always switched to the more effective arm of the trial. They don’t leave you on this arm of the trial thinking well, what the heck, we’ll just leave you there and see how the research pans out. So, they are always switched over to the most effective.

So, I wasn’t really concerned about that. And in the Phase 2 trial, it’s just seeing if the product was effective. And so, that was obviously not a concern for me. So, it worked out, and I do think, though, like what Dana does is absolutely wonderful at totally, totally, totally past wonderful.

But I always try to let people know who have friends and family who are facing some chronic significant illness that don’t just call and say let me know, let me know if I can help you because that’s so ambiguous. And most people will not call because they have pride or they think they can do it all by themselves.

So, I always try to suggest to people that if you’re calling somebody who you think might need some help, be specific. Call and say, “Can I walk the dog? I’m going to the grocery store in an hour. Is there something I can pick up for you? Can I mow the grass?” Anything that will help, but make sure that you are specific in your offering.

Andrew: I want to talk about a related issue. You use the word pride. Some people, maybe in some cases it’s even shame. They developed a certain cancer. Where these are maybe middle-class people who’ve had some resources. They’ve been paying their mortgage. They’ve been paying their expenses, making do. But now they get hit with a cancer diagnosis, which is catastrophic, and there is help available, Dana, but they’re too proud to ask for it when this could happen to anybody. And maybe you’ve even countered that along the way or know there’re people out there. What would you say to people, to not be shamed and to speak up?

Dana: Yeah. Well, sadly, one in three women will be diagnosed with cancer, and one in two men. And so, this is not an uncommon scenario, right? The likelihood of knowing someone who will receive a cancer diagnosis is very likely. So, I think that patients have to understand that pride doesn’t help you in your process with battling this disease. You have to take advantage of every opportunity that’s out there in order to come out on the positive side of this experience. And if you don’t take advantage of every opportunity, you may not.

And so, it’s one of those things that we just have to deal with right from the beginning, and just say okay, again, knowledge is power. I’m going to surround myself or engage with the people that are around me who want to help me. And you have to put that team together because you will need your team with this disease.

Andrew: Okay, so great advice. Reina, part of your team maybe could be the first doctor you saw who gave you the diagnosis, but they might not be the one where a trial was offered. So, first step is you talked about speaking up, but it takes a lot of courage to say to the doctor in the white coat with all the letters after their name, you know, thank you so much, Doctor, and I’ve either found out about a trial, or your turned and typed it in somewhere else. I hope you don’t mind, but I am going to go over there. Maybe you can advise me along the way.

But that takes courage because people are terrified, and they may be bold in principal in that situation with the person in the white coat. What advice would you give?

Reina: Ooh, well, that’s a big one for a lot of people. And, really, you know what, I imagined that it would be people who are older, who come from a generation where the doctor has the final word. But what I found out when I was writing my third book is that there were younger people who also feel very uncomfortable speaking up, asking a doctor, and so forth. But really, what to really put in your little mind and in your heart is this your life.

This is not just kind of a trip to the mall. This is really important for you to either improve the quality of your life or extend the quality of life, so take a deep breath, be very polite, and I think most doctors who are professional and open-minded will hear what you have to say if you present it in a way that they can hear. And if they really don’t hear you then it might be time to have a look around to see who will.

And, really, the bottom line is you need to trust yourself. And if you feel that this is really right, that there is a clinical trial that you would be eligible for and you can participate in with Dana’s help, with the financial, with the logistics, and so forth. Like I said, you just take a deep breath. And most doctors, like I said, really want the best for you.

Andrew: Okay, let’s talk about something that comes up. One of the things for people is the criteria of different trials. Dana, I don’t know if this is in your area, too, related to financial, but people let’s say okay, I wanna be in a trial, but the criteria are so narrow that I really wanna be in the trial, but they say I can’t.

Dana: Yeah, so that is a sad reality in many cases. And I refer to this as Clinical Trial Nirvana Syndrome where as a drug sponsor for trial, you want to attract the healthiest patients you can to participate in your trial, so that you have the greatest chance of success. But, unfortunately, in many instances, in most instances, a cancer diagnosis is accompanied by other comorbidities like heart disease or diabetes or other maladies that would preclude a patient from being able to participate in a trial.

So, that is an area that we are looking into and trying to – we have several proposals out there with various aspects of our government to try and really take a closer look at that, to try and make the trial makeup in relation to patient participants better mirror the realities of our situation because the likelihood of someone, if the drug gets approved, taking that drug and having a comorbidity is pretty likely.

And yet we won’t know what will happen there, right. So, we have to drill down on these issues and it’s a great, great issue to bring up. So, we’ve got a lot of work to do ahead of us.

Andrew: Right. And another thing that comes up too, and Kevin sent in a question. Kevin, thank you for this, matching what’s available in clinical trials to where you are in your journey with an illness. So, on Day 1 you’re diagnosed. I know Esther and I, we were crying and almost on the floor. And I thought I would be dead the next day. And it really took a while to overcome the terror of the diagnosis. And so, we were not even – well, the doctor wasn’t talking about trials; we wouldn’t have been hearing it anyway.

And some of us, thank God, with some trials, with some cancers now, are blessed with living longer and we start to learn. And then we want to know, in our situation, what applies to us. So, I know there are a lot of efforts being made to match trial offerings to where you are and what you might need to know now, what might need to be offering.

And some of you have heard this term, artificial intelligence, where we in the Internet business are all trying to fine tune what we’re suggesting or putting in front of you based on who you are and where you are, recognizing privacy and all those kinda things to make it more manageable.

We still have a long way to go. I mean, we have clinicaltrials.gov, but it’s not tied to where I am, who I am, where I am in my journey. It’s just what’s being done in a certain illness, right, Reina?

Reina: Yes.

Andrew: So, we have to refine our tools.

Reina: Absolutely.

Andrew: We have to refine our tools. Well, we’ve been getting in a number of questions. So, here’s one. So, David; so, he says as the excessive use of CT scans in clinical practice moves away from being the norm, have they lessened their use in clinical trials? In other words, this is about testing, and maybe it’s about the requirements.

Dana, I don’t know if you have feelings about it, but the scientists who are doing these trials, they wanna know everything. They would like to test us. So, the CT scan, and I mean I’m gonna have one next week, but it has radiation, right?

Dana: Right.

Andrew: So, let’s do a bunch of CT scans. No, let’s do a bunch of bone marrow biopsies. No. So, I’m saying I’m sorry. Not just do I have to pay something for these tests, or is there a co-pay or whatever, but also am I gonna be radiated? Am I gonna be poked? So, what about those issues? Is there dialogue going on, not just to help us financially, but also make it less onerous, I guess?

Dana: Yes, in fact there is dialogue going on about that, and it’s good, heartfelt dialogue. And it’s coming from a myriad of stakeholders, right, not just from patient advocacy organizations, but also from within industry insurers. And the whole goal is to okay, let’s stop looking at patients as a chart or a number on a piece of paper, and let’s understand that these are living, breathing human beings who are voluntarily participating in this clinical trial process for the benefit of not only themselves, but future patients to come and our industry.

And let’s start treating patients as humans who are participating, and let’s see what we can do to lessen the number of visits or minimize the number of scans and blood work, et cetera. So, there is active dialogue around that, and I think there’s a much higher degree of sensitivity on behalf of the teams who are actually putting the protocols together now.

Andrew: All right, I think so. And I know in some cases they’re doing what’s called trial simulations with a panel of patients and saying okay, we’re trying to answer these scientific questions and see if this drug that’s in development can do better for patients and would require so many office visits. Or so many, you come to the site, but so many could be done, maybe with your local doctor if that’s closer to home. So many blood tests, so many CT scans, so many biopsies. Imagine lung cancer patients with another lung biopsy. Not fun, and often not available.

So, there are all these kind of questions. And I think that’s going on although it needs to happen more. Now Dana, do you talk to the pharmaceutical industry? We had a question from Vi Life wanting to know related to trial awareness. Beyond the financial, do you work with pharmaceutical companies at all, as you are now, today? I mean, what we’re doing here is just to raise awareness about trials or other programs that you may do.

Dana: So, we are engaging with pharma right now. We were very fortunate to work with the FDA earlier this year in securing language around reimbursement of patients’ out-of-pocket expenses associated with clinical trials. There was some very nebulous language out there that was really preventing pharma from being able to support programs like ours.

And what we’re doing now is, in addition to we’re bridging this gap for patients that exist every day by reimbursing patients, but that is not a sustainable business model. It’s noble, but we have to have our tin cup out every day. And the number of patients we can help is directly related to the amount of money that we have in our account, right?

So, in addition to that program, our Lazarex Care Program, what we are also doing is trying to fix this problem and do it in a sustainable way. And in order to do that, we actually have to shift the burden from the patient back into industry, right, and help industry understand why they should include these out-of-pocket expenses as part of the clinical trial protocol every time, right, so they can enroll trials on time, on budget, save R&D dollars, preserve patent years, right?

I mean, there are a lot of reasons why pharma would want to participate in a program like that, in addition to the fact that it’s the right thing to do, right? And then we get more drugs to market faster, and we provide a platform of equitable access for everyone. So, we are engaging pharma in discussions right now about funding this program, we call Lazarex our IMPACT Program, that’s being rolled out at comprehensive cancer centers across the country. And it stands for Improving Patient Access to Cancer Clinical Trials.

It has been received very well and I’m happy to say that Amgen actually stepped up and funded this, so we are rolling it out here in California, and we are hoping that we’ll have similar opportunities in a couple of other areas in the United States. So, they are interested, and they want to improve clinical trial enrollment retention, and especially minority participation.

Andrew: Right. Boy, that you. Again, I keep saying thank you for what you’re doing, but you’re a real leader in the field. I’m going back next month to the Biden Cancer Initiative Summit continued by Vice President, Biden, former Vice President Biden, and his wife who continue to do leadership in this. And there’ll be a lot of senior people there and I’m hoping we can talk. And I know this issue of how can we advance cancer care through research in partnership with patients is a big one. So, Dana, thank you for helping lead the way in getting this going. And thanks to Amgen just as an example.

Reina, so, we talked about the cultural differences of people being in trials. We talked about the pride people may have in asking for assistance, the fear people have maybe participating in trials. You still have a – not now. I mean, you’re doing so well and you’ve been through trials and it’s worked out well. But there must have been some bumps along the way. Were there any misgivings at different times? And if so, how did you overcome it?

Reina: Oh, yeah. Well, there were definitely misgivings, I am sure. The first trial was when I asked the doctor if there’s something going on at the NCI. And there was no misgivings about that because that was a very observational trial. The second trial was much more progressive and I felt kind of a little uncertain about it, and so I asked the researcher at this well-known institution if I should participate because the trial, I should back up a little bit, that was for either smoldering myeloma patients or active disease patients.

At the time I was smoldering, and most physicians didn’t believe that that was a good idea to treat smoldering and wait until it became active. So, I asked this one researcher and he said absolutely, not, do not participate in the trial. And then I called someone else also from a very respected institution where I had been, and he said well, if you join that trial you’ll be crossing the Rubicon, which I didn’t even know what the Rubicon was at the time. I had to go look it up.

But, basically, once you start treatment, you kind of go on that journey and there’s no way to step off. But then I thought about it, I thought about it, thought about it, and finally I decided to trust myself because I had been to the NCI. I felt very safe there. And I decided to move ahead with it.

So, yes, I had plenty of misgivings about that. The other trials, not really because that trial changed my life and it gave me a very reasonable complete response. And the other ones, like I said, they just kinda fell in with the collecting a good amount of stem cells for a transplant and so forth.

Andrew: I wanna talk about family issues. So, the decision to be in a trial affects the family, whether it’s somebody’s driving you to the doctor, somebody’s taking off work, their worry, how they feel about trials, their own view of it, family logistics, costs, et cetera. We’ve talked about that. So, you wrote this blog about people questioning your husband, I guess, was your wife gonna be in a trial? So, how did you overcome that, whether if not with your husband, just with your community that you weren’t like crazy?

Reina: Well, they already know I’m crazy, so that’s a total aside. But, really, trying to educate people about the misinformation about trials; say, look, I will never be a guinea pig because that’s not what trials are about. And it’s very well controlled and there’s a lot of data that follows you. The care that I got was excellent.

And I try to dispel, like I said, a lot of the myths; that you signed consent form, which clearly explains what the trial is about, what your commitment to it is, and you can also drop out for any reason. There was hope that you don’t because they would like to have some results that then will lead into future treatments for patients. But you can drop out, so, really, taking that opportunity to educate people about what a clinical trial is like and that there are no guinea pigs.

Andrew: I wanna just – oh, yes, please, Dana.

Dana: Yeah, if I could just offer something in that regard. For people who haven’t gone down this path, the journey with cancer, having a cancer diagnosis is not like other chronic diseases, right, like diabetes, for instance, that you can typically control with insulin or whatever, right? For a cancer patient who has failed standard of care, who’s gone through maybe second- or third-line treatment options, but still has progressive disease, that patient will die if they don’t do something, right?

And so, clinical trials offer tomorrow cures today in some instances, right, and we don’t always have positive results in clinical trials. But for a patient who’s at that crossroad where their doctor has delivered those words, “You need to get your affairs in order,” right, it’s not a matter of am I crazy if I participate in a clinical trial. What it is a matter of is do I wanna live? And if so, what clinical trial can I participate in? It’s a very different decision tree.

Andrew: Right. And I certainly say that all the time. I got a call, as I mentioned, from a friend in Miami. The mother has a very serious cancer. And I said part of the initial discussion, even the initial discussion, Dana, can also be are there clinical trials that we should consider along with standard therapy? So, certainly, if you’ve failed or they’ve failed you, the treatments no longer work, what is the 360 degree view? And if you don’t do it here, so they do it down the road, or do they do it across the country? And what are the issues for you participating?

So, a lot of thinking, but it’s gotta be part of the discussion. So, so sadly now, what are we seeing; 3 percent, 4 percent, 5 percent of adults participating in cancer clinical trials in the US. Not good at all. And are we hurting ourselves with the chance of future therapies that can be more effective, or even cures because some of these companies sometimes are venture-backed. They don’t have money forever, you know, and they’re trying to get to the goal line to go the FDA.

Look, here is another question we got in. Tamara, our producer, just sent in. She says well, what happens when you join a clinical trial and it doesn’t have a beneficial impact? So, Reina, they didn’t know that the trials would necessarily work out for you. So, what happens then? Do you go on another trial? What do you do?

Reina: Well, if it doesn’t and you don’t seem to be responding to the therapy on the trial, or you find it intolerable yourself, then they will always return you to your oncologist who you had been seeing previously. But, on the other hand, they may offer you another trial that’s available that you would be eligible for as well. So, I mean, I really try to stress to people that the researchers are looking out for you. They want the best income, in addition to accruing the data that they hope.

And I can tell you that when I was on a trial at the National Cancer Institute, when I had questions, especially about the trial with smoldering versus active disease for myeloma, they would spend a couple of hours for me, explained with me, can I say that, right? Yes, spent a couple hours with me explaining all of the aspects of the trial, so yeah.

Andrew: I wanna point up an example that some people have heard of a woman I’ve become friendly with in the myeloma community, Reina. Cherie Rineker. So, Cherie’s down in Houston, and she was dying of myeloma. And she’d been in trials and treatments. She was at MD Anderson. Bob Orlowski is one of the top doctors in the world, and her doctor. And she was in different trials and then things were not working.

And she was put in touch with another researcher doing this CAR T investigation for multiple myeloma, which is pretty new, pretty new. And they’re learning a lot. It’s not a slam dunk, but so far it’s worked for her. It saved her life. She went to Nashville, Tennessee from Houston where she lives, and maybe I’m not sure the financial issues, Dana, about going. But that’s where she’d been in successive trials. And some were not working or no longer were working. There was another approach.

I wanna ask about another concept I’ve heard called siteless trials. And I don’t know, Dana, you’re nodding your head. Maybe you are familiar with this. One is a siteless trial because we talked about these trials going on at these academic medical centers, but not much elsewhere.

Dana: So, I have tell you, I don’t have a lot of experience with siteless trials, but there is a lot of dialogue taking place around rather than having the patient go to the trial, bringing the trial to the patient, and I think that’s the impetus behind a siteless clinical trial.

I think cancer has some unique challenges, especially blood-based cancers in clinical trials, and the oversight of patients participating in those trials that make siteless trials a bit of a challenge. But I think the place to start is in other diseases, or perhaps where you have a cancer diagnosis that’s not a rare form of cancer, whatever that requires, a high degree of oversight.

But the whole goal in doing this is to understand how we can get more people into these trials and make it less obtrusive on their life, right, so that more patients would be inclined to participate, increase our enrollment retention, our minority participation, and, ultimately, reduce the burden on the patient to participate.

Andrew: Esther and I’ve given a lot of talks at different conferences, and we said you have to see patients who might be considering or are in a trial as investors. So, they’re gonna invest with their body, their time, sacrifices, and other things in their lives for the hope of being cured if they could, or doing better.

And there needs to be the communication, financial support, logistical support in really treating people with a lot of respect as a person. Reina, do you agree with that, that we have to get to that concept where we’re taken care of? And you felt that way, but we need to do it for more people and have more people feel confident that it’ll work out that way.

Reina: Oh, certainly. Certainly, I do. And the education is really essential. And after I was in the first trial, I talked to everybody who would listen to me. And even if they didn’t, I would talk anyway just to try to say this is a place where you can go where you will receive what is hopefully the newest and the best treatment that’s available. That you will be cared for as well as you can possibly be, and that everything is documented. You know all the options that you have staying on the trial, giving consent, making sure you have all the information that you need to feel comfortable.

And Dana’s organization, hopefully, helping people out financially and logistically. There are ways to get into trials that at times are very successful. For me personally, I don’t know that I would be alive now if I had been on that trial, and that’s really my claim to fame, what can I say?

Andrew: And, Reina, I would say the same thing. Had I not been in a Phase 2 trial for chronic lymphocytic leukemia in 2000, I wouldn’t be around to have had retreatment last year, which has work quite well; 17-year remission. And I wouldn’t have been able to do this, and really have a purpose in life. So, I’m very grateful for being in the trial.

Dana, I can’t tell you – we were talking about gratitude, for you; came up in your family. You saw the gap for, not so much your family, but so many other families. The issues, financial issues, and you’ve been very philanthropic and, obviously, trying to have leadership in getting at some of these – we have a very imperfect system right now, so we have a long way to go. But for our viewers, if you’re living with cancer now, if your loved one is living with cancer, there are resources, people like Lazarex, people have been through it, like Reina.

We’re gonna give you this downloadable guide. And you’re gonna connect with these resources. Don’t… Put your pride away. Dana said it so well. There’s a very high likelihood we’re gonna be affected by cancer in our families, and there is help to navigate what’s kinda complicated right now, but is doable and can offer you the chance of doing better. Dana, did I say it right?

Dana: You did. You did. You did a great job, Andrew. Thanks.

Andrew: Okay. Well, thank you. And thanks to the Lazarex Cancer Foundation and, really, all you’re doing. And let’s hope that we can improve this process, increase participation, and have so many of these companies and the government that are trying to get scientific answers. We participate as respected patient investors. And we do better well. Reina, any final words from you with your 50th wedding anniversary coming up?

Reina: I’m very grateful. I’m very grateful to be here. I’m grateful for all the clinical trials, all the physicians who have taken care of me and who listened to all my concerns and fears. And I am super-duper grateful to my husband who has supported me, helped me, been there, been my caregiver, and washed the food for me when I had the transplant, and really, all the people who have been on the journey with me. So, if you are considering a clinical trial, if there is one that you might be eligible for, give it some thought. It’s a really important choice for you to make.

Andrew: Reina, thank you so much, all the best. Happy anniversary, early. Dana, best to you. Dana Dornsife, joining us from the Lazarex Cancer Foundation in the San Francisco Bay area. Dana, good health to your family, and thank you for all you do. Thanks for being with us, Dana.

Dana: Thank you.

Andrew: And, Reina, all the best, and thank you for those great words of wisdom. And we’ll meet in person sometime and I’ll give you a big hug, okay?

Reina: I hope so. I hope so. You take care of yourself, Andrew. Thank you so much.

Andrew: Thank you for joining us for this Patient Empowerment Network program Clinical Trials Mythbusters. We hope to do more. I wanna thank the companies that have helped provide funding for it; Abbvie Incorporated, Astellas, Celgene, and Novartis, for their support.

Thank you for joining us. I’m Andrew Schorr from Patient Power down near San Diego. Remember, knowledge can be the best medicine of all.

Reinventing the Clinical Trial: Start at Ground Level

If each of us humans is a snowflake, unique in our genomic makeup, where’s my snowflake medicine? I asked that question from the platform at the ePharma Summit in New York in 2013, and have yet to get an answer. The challenge for the bioscience industry is, I believe, the classic randomized clinical trial. That design goes through four phases:

  • Phase 1: a small group of people are given the drug under study evaluate its safety, determine a safe dosage range, and identify side effects
  • Phase 2: a larger group is given the drug to evaluate its efficacy and safety in a larger population
  • Phase 3: large groups – plural – of people are given the drug to confirm its effectiveness, monitor side effects, compare it to other commonly-used treatments, and collect information that will allow the drug /treatment to be used safely
  • Phase 4: the drug is marketed while study continues to assess long-term effects and efficacy

Of course, before they even get to Phase 1, there have to be both the idea for the new treatment, and animal studies to determine what the substance or compound under study might do to a mouse or a monkey.

Science isn’t easy. The phrase “trial and error” came out of science labs, with many trials running up against the error wall by Phase 2. Since bioscience companies can sink about $1 billion-with-a-B into getting just one drug to market, it seems that the traditional clinical trial has turned into a pathway to NOT making scientific discoveries that can benefit humankind.

Then there’s the whole “who’s in charge here?” question. Clinical trials are now a global effort, with US and European pharma companies testing new treatments in Latin America, Russia, and China to gain traction in those emerging markets while simultaneously developing me-too drugs for their domestic markets. So, who’s in charge, the US Food and Drug Administration (FDA)? The European Medicines Agency (EMEA)? A player to be named later? The answer to the question seems to be “all of the above,” which adds to the complexity of the clinical trial process.

As digital technology has made data easier to collect and share, it would seem that clinical trials would be a great place to start intersecting with the quantified-self movement. The shift to electronic health records, the widening adoption of all sorts of health tracking devices, and the rise of (relatively) cheap genomic sequencing should signal an ability to identify conditions, and populations, eager to participate in clinical investigations. But so far, it hasn’t.

What might challenge that stasis? In November 2013, three major pharma companies – Novartis, Pfizer, and Eli Lilly – announced via the White House’s website that they had joined together in a clinical open innovation effort. That page on the White House’s site is gone now – changes in Presidential administrations will do that – but here’s a direct quote from that announcement:

“In order to connect patients and researchers, Novartis, Pfizer and Eli Lilly and Company, are partnering in the U.S. to provide a new platform to improve access to information about clinical trials. The platform will enhance clinicaltrials.gov and will provide more detailed and patient-friendly information about the trials, including a machine readable ‘target health profile’ to improve the ability of healthcare software to match individual health profiles to applicable clinical trials. As part of the project, patients can search for trials using their own Blue Button data.”

Five years later, and we’re still stuck on the slow train when it comes to really reinventing the clinical trial.

I’m one of a growing group of people who think that the entire life-sciences process chain needs to be re-tooled for the 21st century. In my view, the best place to start that re-tool is at ground level, with the patients and clinicians who deal with challenging medical conditions daily. If a doctor has a number of patients who might benefit from some clinical study, why isn’t there an easy way to find a researcher looking into that condition? If a patient has an idea for a clinical investigation into his or her illness or condition, why can’t they find a researcher who’s interested in the same condition to team up and start a science project?

I can only hope that the regulatory agencies involved in life science oversight (hello, FDA!) can move beyond the aftermath of Thalidomide – for which epic disaster we’re still paying a price when it comes to the timeline for drug approval in the US – and toward a process of “all deliberate speed” that doesn’t forsake speed for deliberation. Both are necessary, neither should be more heavily weighted than the other.

We all can, and should, take part in scientific exploration into human life, and human health. Got an idea for a clinical trial? Share that idea in the patient communities you hang out in, and ask your tribe to help you bring that trial to life. To quote Arthur Ashe, “Start where you are. Use what you have. Do what you can.”

We’ve got to start somewhere, right?

Talking To Your Family About Clinical Trial Decisions

Hearing your name and the word “cancer” in the same sentence is a world-shaking moment. After getting a cancer diagnosis, telling your family about it is another big step, one that can be fraught with as much emotion as hearing that diagnosis yourself.

Once the emotional dust has settled, talking with your family about treatment options, including clinical trials, can raise the emotional temperature again. If your family is like mine, everyone has an opinion, and is more than ready to share it. Even in families where everyone is calm about big issues like this – I question that those families exist, but I’ve heard they might – talking about clinical trials as a treatment option means being ready to field questions, and guide the conversation.

The American Cancer Society has a great set of resources for people who are assessing whether clinical trials are a good option for their treatment. I’ll use some of those as a framework for a discussion guide you can use to walk your family through your decision to explore clinical trials for your cancer:

  • Why do I want to participate in a clinical trial?
    • Your reasons can be anything from “I want to try cutting edge treatments” to “my cancer is advanced stage, and I want to throw everything but the kitchen sink at it.” The key here is to have an answer ready to this question when you discuss treatment options with your family.What are the risks?
  • What are the risks?
    • Here’s another question you’ll want to gather answers for, for yourself, before opening a conversation with your family about enrolling in a trial. Your oncology team can help you put together a risk profile for trials, and further help you target the right trials via molecular profiling of your cancer.
  • Will my insurance cover the trial?
    • Federal law requires that most insurers cover routine costs of cancer trials. However, like so much about US health insurance, the answer can still be “it depends.” There’s a great tip-sheet on the National Cancer Institute’s site that addresses this topic. You, and your family, and your oncology team, will be working together to make sure your costs are covered, either by your insurer or the trial sponsor.
  • What happens if I’m harmed by the trial – what treatment will I be entitled to?
    • Here’s another “it depends” situation. Addressing harm to trial participants is an ongoing ethics issue in the US. The key here is to review all trial enrollment documentation fully – with help from a medical ethicist or legal eagle who’s not involved with the trial, or your oncology team – and have any potential harm scenario fully spelled out, including who will address the remedy for harm, and how that remedy will be delivered.

Having solid family support is a key factor in managing cancer treatment, and in thriving as a cancer survivor. Getting your family involved in your care by talking through your options and decisions with them will give them a sense of involvement in your care, and its outcome. They can help you through the down days when side effects have you feeling punky, and celebrate the bright days with you when scans show progress against your cancer.

Curing cancer is a team sport. You, your family, and your oncologists are all on that team. Work together toward a win, which often includes unlocking the power of precision medicine via clinical trials – which can become a win for other cancer patients, too.

Clinical Trial Mythbusters: Does the Clinical Trial Process Need an Extreme Makeover?

Does the Clinical Trial Process Need an Extreme Makeover?

Clinical Trial Mythbusters: Does the Clinical Trial Process Need an Extreme Makeover? from Patient Empowerment Network on Vimeo.

Downloadable Program Guide

Many cancer patients feel that the clinical trial process is in need of a serious makeover. One of them is Jim Omel. Jim, a retired oncologist living with multiple myeloma, turned patient advocate, makes it his business to understand myeloma from the inside out. He joins this program to share his experience in clinical trials and how he learned about his vulnerabilities as a cancer patient.

Also joining the discussion is, Dr. Michael Thompson, medical director for the Early Phase Cancer Research Program at the Aurora Research Institute and an active clinical researcher developing new treatments, particularly early phase (Phase I and II) molecular biomarker-driven clinical trials.

Join us for a meeting of the minds on debunking myths around clinical trials. How are patients protected within a trial? Will I as a patient be lost in the clinical trial system? Can I select my own arm in a trial? The questions are endless and, left unanswered, contribute to the barriers to trial enrollment.


Transcript:

Andrew Schorr:

Welcome to this Patient Empowerment Network program. I’m Andrew Schorr from Patient Power. I’m joining you from near San Diego, Carlsbad, California, and I’m so excited about this program, Does the Clinical Trial Process Need an Extreme Makeover? Having been in a clinical trial, and I’ll talk about my experience in a little while. I am a big fan, but I know that people have concerns, and I know that the percentage of cancer patients who are in clinical trials among adults is very low. How does that affect drug development and having the chance to get closer to cures for us?

I want to thank the financial sponsors for this program who provided assistance to the Patient Empowerment Network. They are Celgene Corporation, Astellas and Novartis. They have no editorial control, so what happens in the next hour is what we say, the questions you ask, what we hear from our experts who are joining us.

If you have a question, send it in to questions@patientpower.info. Again, if you have a question, send it in to questions@patientpower.info, and our wonderful producer Tamara will take a look at it, forward it to me, and as we can over the next hour we’ll be discussing questions you have already sent in. And we’ll have a very inspiring, I think, and provocative dialogue between our experts.

So let’s meet them. I want to take you to Grand Island, Nebraska, where my dear friend Jim Omel is there. He’s a retired now family practice physician. And, Jim, for years you’ve been a myeloma patient. When were you diagnosed with myeloma, and what’s happened along the way? You’re taking regular treatment now, I think, some treatment for the bone complications. How are you doing, and when were you diagnosed?

Jim Omel:

Andrew, I was diagnosed in 1997. It started off with a plasma cytoma at T10. I broke my back, I underwent a stem cell transplant in 2000 and had six years of remission. It came back in 2006, and I had radiation and lenalidomide (Revlimid), and it went away a while. Came back again in 2010, and I had radiation, bortezomib (Velcade), Revlimid, dex, and it went into remission. And since then, Andrew, I’ve been so fortunate that all I’ve been taking is bone-protective bisphosphonates.

Andrew Schorr:

Oh, good for you. Now, you were in a trial, but you decided not to continue, but yet you’re a believer in trials.

Jim Omel:

Oh, absolutely. Without trials our treatment wouldn’t change. When I had a full evaluation at Arkansas they suggested that I join their trial, and I did, and at the end of that trial was a tandem transplant. And I got to thinking and reading, and I didn’t really want to get that extent of treatment. I had a single transplant, and I dropped out of the trial. And that’s one of the things that I would certainly tell our listeners, that they can stop a trial at any time. They’re not bound to it. Ever since then, Andrew, I’ve had the good fortune of having fairly responsive myeloma, and when I had my treatments they responded to standard therapy. I certainly would have rejoined another trial if necessary, but I was fortunate that it responded the way it did.

Andrew Schorr:

Okay. And before we meet our next guest, I just wanted you to list some of the committees you’re on, because you’re very active locally and nationally on behalf of patients. So what are some of those activities you’re doing?

Jim Omel:

Well, I’ve been doing this since about 2000, so that involves a lot of activity. Peer review with the NCI was one of my main ways to get started.

Andrew Schorr:

National Cancer Institute.

Jim Omel:

Yes, and I progressed on to the Board of Scientific Advisors, which was a really good, important work with the director of the NCI. I’ve been an FDA patient representative for many years and was on the advisory board that brought Kyprolis or carfilzomib to us. I spend a lot of time each month for sure with the Alliance Cooperative Group working with Paul Richardson as we bring you new trials to patients. I’ve been with CINBR, Center for National Bone Marrow Transplant research for several years, several advisory boards. I’m on two pharma accompany advisory boards as they seek patient input.

Andrew Schorr:

Wow. All right. Well, the point of this, what I wanted our viewers to get, is that Jim is—trained as a physician, worked many years as a family physician, became a patient, eventually had to retire. He’s been through a lot of treatment and is very much an advocate for all of us, particularly in this process of trials. So we’re going to talk about the unvarnished truth about trials and see how we can make it better. Okay.

Let’s skip over to Milwaukee, Wisconsin, where we’re joined by Dr. Mike Thomson, who is very involved in research, and Mike has been very involved in all sorts of programs related to education. So, Mike, first of all, welcome to the program, and tell us a little bit about your involvement both locally in research and in education of other physicians nationwide and worldwide.

Dr. Thompson:

Sure. So not as impressive as Jim, but he’s one of my heroes who has really dedicated himself to improving the clinical trials process. I have an MD, PhD. My PhD is in pharmacology, and I was interested in pharmacogenetics and how individuals vary in their response to drugs, especially cancer drugs. I did my fellowship at MD Anderson and worked with a lot of myeloma doctors there and have worked in the community setting seven years in one place and about five years now where I’m located at and Aurora Healthcare in Milwaukee. I have been on the NCI Myeloma Steering Committee. I’m currently on the NCI lymphoma steering committee. I helped organize the ASCO 2016 meeting. I was the Chair of Education. As of June, I’m one of the editors for cancer.net around myeloma, so taking over from Paul Richardson who did that. So I’ll have about three years doing that and probably asking people like Jim for help to provide educational materials for people. And in the world of myeloma, I’ve created the MMSM or Multiple Myeloma Social Media hashtag to have Twitter chats, which I know some people don’t think are the optimal form of communication, but it is a way to get information out from experts and some opportunity for patients to ask questions. So I’ve been highly involved in social media, highly involved in the NCI and NCORP for increasing access to clinical trials in the community. And right now I am in the middle of an NCI designated clinical trial called EAA172 for multiple myeloma, which has gone through ECOG Executive Committee, the NCI Myeloma Steering Committee, and now we’re discussing with the companies and with Ctap how to bring that forward. And I think that’s—one of the things is how much effort it takes to bring some of these trials from concept to activation.

Andrew Schorr:

Okay. Now, we’ve mentioned this more rare cancer, multiple myeloma, not rare if you have it, but Jim has it, Mike specializes in it a lot. But what we’re talking about applies to the clinical trial process about broadly. So we may have people with us living with lung cancer and hoping to live longer and better, prostate cancer, chronic lymphocytic leukemia, like me, are also myelofibrosis. I’m a two-fer, if you will. There may be many different cancers among our audience, and the process applies to all. So we’re going to talk about that. So whatever it is, ask your questions, questions@patientpower.info. I’m just going to share a little personal story for a second, because I’m very passionate about it, and I wanted to mention it. And this is part of our Clinical Trials MythBusters series, and we have previous programs on Patient Power with lung cancer experts, experts in other conditions about the clinical trial process, so look that up on patientpower.info. There will be a replay of today’s program and also a downloadable guide with highlights that you can share, talk about it with your doctor, with other patients, with people you know and for your review. Okay.

So now my own story. I was diagnosed with chronic lymphocytic leukemia, the most common adult leukemia, in 1996—terrified, had no idea what it was. Didn’t know anything about what a trial was, didn’t know what the treatments were. Quite frankly, thought I’d be dead like within a week. I didn’t know. And so you start getting educated, and eventually that led to me connecting with academic medicine specialists and ultimately suggestion at the appropriate time of being in a Phase II clinical trial. I didn’t know what the phases were, we may talk about that along the way, and it was 2,000 miles from my house. So I traveled a number of times to be in that trial, and I had my local oncologist collaborating on that. And the end result was I had a 17-year remission. I had treatment again for chronic lymphocytic leukemia. It wasn’t until last year, 17 years. And I got the combination of medicines 10 years before that combination was approved. So I’m a believer.

The second thing I’d say about trials was I was in a second trial along the way, and I had deep vein thrombosis, blockages in the veins in my legs, for a blood thinner trial. And by being observed in that trial, that led to them discovering a second cancer which was at work related to those clots, myelofibrosis, and I was observed, so I liked the attention. It had nothing to do with what they were testing. It had to do with the observation you get. So, again, I love the attention of being in a trial. It may give you access to tomorrow’s medicine today, but there are things that may be broken. So, Jim, let’s start with that. Jim, what has been some of the frustration points for you the way the process has been today?

Jim Omel:

Well, I think one of the main things, Andrew, is that clinical trials tend to be designed to answer scientific questions. I think what they should do is be patient friendly. I think they should be designed to help patients. If you ask any researcher, what is the purpose of the scientific trial, clinical trial, they will say, to answer a question. If you ask a patient, they’ll think the purpose of the trial is to help patients. The—it may seem like a minor point, but it’s not. Patients need to be the center of them. We need to help patients understand what their contribution is to a trial. For instance, hardly ever does a patient hear how their outcome, what they did during a trial improved the final outcome of a trial. The patient needs to be centered. If we get the trial to a point where some of the questions are pretty obviously answered, rather than continuing to recruit patients just to be statistically valid, I think trials should close sooner. I think they should be more focused on getting patient care without necessarily the scientific question. I’m not a radical. I’m certainly a fan of trials. We wouldn’t be where we’re at without trials, but I think they should just become more patient-centered and patient-friendly.

Andrew Schorr:

Okay. Now, Mike, Dr. Thomson, so we know we can’t have new drugs approved by the FDA unless there are trials, Phase I, Phase II for sure, and often, typically, Phase III and sometimes even monitoring after a drug has been approved. I think you call those Phase IV trials. But from where you sit having been around this a long time what are some of your frustrations? What would you like to see be improved?

Dr. Thompson:

I agree a lot with Jim. I think another word to put on it is pragmatic trials. So I’ve been on a number of advisory committees, NCI investigator-initiated studies and pharma-directed studies. And when you have an advisory group with a bunch of academics they often think about the theories, and they think about what would be interesting to know. And increasingly both the NCI and others are getting not only patients but community physicians who will say I don’t really care about this question here. And we don’t think that it will fly and won’t accrue, and we know a lot of trials don’t complete accrual, so therefore patients are wasted, if you will, because we won’t have the information, we won’t be able to answer questions. So I agree. There are so many things get to involved it’s hard to break them all down, but part of the issue is answering a clinically meaningful question. I think the meaning should be patient-centered. Within those questions you can ask scientific questions that are imbedded in what are sometimes called secondary imports or co-relative studies. But I just last week was talking to some pharmaceutical leaders, and I said, you have to design a trial to answer a question people care about, and that’s patients and physicians. Because sometimes the trials are designed to get FDA approval, and they’re comparator arm if it’s a randomized study, is an arm that we don’t think is the current standard of care, and we have to do them in countries where they don’t have as many therapies and they don’t have as much access, so they’ll get them done. But then when they’re approved in the U.S. we don’t know what to do with the trial, because it’s not a question we’re asking. So that’s important. And I think if more studies are done not to get FDA approval but to go on pathways and to ask, what are the clinical branch points for decision-making, I think that’s when you’ll start getting good trials.

There are a number of other issues around the pragmatics. So there’s this NCI Match study, tons of people screened, very few people on the matched drugs, and they switched over to a strategy more like an ASCO TAPUR, where they waited for people that already had testing and then the people that had already kind of pre-screened couldn’t get evaluated for the study. And many, many more people went on study. The imaging and other things in the middle were not as rigorous as a usual clinical trial. It rolled quickly, and I think the point is you’re looking for big end points. Where you have to sort of go back to the classical, randomized, Phase III large study is when you’re trying to make incremental improvements, so, for instance, breast cancer where the cure rate or progression-free survival rate may be in the 90-something percentile rate, or even CML or other things where we’re doing so well you’d need a lot of patients and probably a standard design. But in many other areas you can do a variety of different techniques—Bayesian analysis, continuous reassessment models.

And one thing Jim mentioned was stopping for futility or if there’s an obvious benefit, and that is done but probably not as often as it should be. And the designs using what are called interim analyses or futility analysis with data safety monitoring boards or DSMBs, probably could be more robust. There could be more of them. I think people are afraid to do them, because they do slow the trial down, they slow accrual, and that has to do with stuff both within the trial as well as extrinsic to it. So there are a number of barriers and issues, but I think Jim’s pinpointed them as well.

Andrew Schorr:

Okay. Well, folks, you can tell that Dr. Thomson is a scientist. We’re going to unpack this and get down to the nitty-gritty. So, okay. So, Jim, so first of all, we mentioned this term “randomization.” So people wonder in cancer am I going to get the good stuff? I know that I’m sick, maybe like in your area, multiple myeloma, there have been lots of new medicines, but in some other areas not, like pancreatic cancer, for example.

So, say, I understand the standard therapy, and you’re testing it maybe against that, but I want to get the good stuff, because I’m really hopeful. I want to be a believer. So could you just describe where we are with randomization, because that’s a concern people have?

Dr. Thompson:

Absolutely, Andrew, and thanks for asking that question. That’s a real red, red hot button item for me. I maintain that if the patient has gone through the effort of studying their cancer, studying the possible treatments, and they’ve learned of a trial that’s opened that they would qualify for, they’re excited, they go talk to the principal investigator, and they say I want to be in this trial. And the PI turns to them and they say, well, we’ll flip a coin. You may get the medicine we’re going to be using, or you may get standard therapy. Just imagine how disappointing that would be. And when it comes to randomization, Andrew, there’s many, there are many trials that absolutely lack equipoise. And I’m afraid that scientists often use equipoise.

Andrew Schorr:

Now, tell us what that means. You’ve got to define that for us.

Jim Omel:

Equipoise basically means equal, equal balance within the arms. In other words, technically, officially the principal investigator doesn’t know which arm is best. And yet look at it from the patient’s standpoint. Let me give you an example. There was a trial in which patients had the choice of three oral drugs in one arm versus a stem cell transplant in another arm. Now, think about that. Think of the insurance ramifications. Think of the fact that it takes almost a year to really totally recover from a stem cell transplant, versus taking three oral drugs. How can anyone say that there’s equipoise in a trial like that? So how can you pattern your life with the flip of the coin or a computer randomizing you into one of those arms?

Andrew Schorr:

Wow. That’s, that’s an important issue. Another one is, Mike, you know, people are—one of the ladies wrote in on Facebook I posted about this program, and she said, well, the trials are not really accessible to me because I live in a rural area, and they’re only in the big cities. You’re in one, Milwaukee. But Jim’s in Grand Island, Nebraska, and some people if you set requirements for the trial, well, you’ve got to come see me, you’ve got to come to the clinic for a variety of tests with some frequency and somebody has to drive four or five hours and take off work and get babysitters and all that, it just makes it impractical. Where are we with more trials being available or having an aspect of it, like testing, closer to home?

Dr. Thompson:

So I work at a community setting. I’m at our kind of flagship hospital but we cover most of the population centers of Wisconsin, so I think we cover about 70 or 80 percent of the population. So that’s a huge issue for our site is that we—when I talk to sponsors including as recently as last week I say if we can’t do it at all our sites I’m not really interested in doing your trial.

There are exceptions of course. We’re doing a surgical trial or a radiation trial that has to be at one site or sometimes a Phase I trial with just a lot of blood monitoring, very intensive, they can only be done at a few sites. But in general I completely agree that we should try to have the drugs available to people in the community they live in, because that’s where their social networks are, right? So that’s where their family is. They can stay at home. They don’t have to just go into a hotel. They don’t have to pay for travel, and I think it’s better for everyone. And for companies, I’ve been trying to tell them that it’s more generalizable to the reality of where cancer patients are. So

85 percent of cancer patients are in the community setting and are treated there, and drugs should be accessible to them there. So, you know, both the using the CCOP mechanism or NCCCP, and now we have the NCI Community and College Research Program or NCORP. The whole idea is to increase that access to community sites. So this has been going on a long time. I think there were budget cuts, and so the U.S. and the way we’ve established our cancer budgets has been to decrease access at least NCI trials and usually need some of those NCI trials to support the research infrastructure to do other studies. So I think part of that, you know, a lot of these things you follow the money. And if there was more money for community research sites, you could hire more research staff to get these things done.

But I think we need to get them done in the community, because we know if you do early phase studies and they look promising in highly selective patients, then when you expand them and put them in the community you go from efficacy to effectiveness, and the effectiveness isn’t there because the patients are different. So there are all these things with real-world data and comparative effectiveness research at ASCO’s cancer link trying to get at some of that not on study to just try to get the data.

But we need to have access to people, and the way to make drugs cheaper, make them develop faster and answer more questions, both scientific and patient-oriented, is to get more people on trial. There’s a big example for immunotherapy drugs where there are so many immunotherapy drugs and trials there are not enough patients to get it done. So we’re going to enrolling in trials which don’t complete, or we’re not going to be able to answer these questions, so it’s going to stall and move it out the process of moving faster. In myeloma, we move very fast, but we need to do this in other areas too.

Andrew Schorr:

Right. So let’s talk about that. So, Jim, you know, the president had a big kick-off, HHS Secretary Azar I think just yesterday as we do this program, was before Congress and part of it was the discussion of can we lower the cost of drugs ultimately? And one aspect of it is can we speed drug development. So instead of all these trials languishing at the cost of millions of dollars, hundreds of millions of dollars, how do we speed it up?

So one is participation, certainly, but can the process be simplified as well, Jim? What work is going on there, so we can try to get these answers and get to the FDA and present the data quicker, and hopefully there’s been lower cost in getting to that point?

Jim Omel:

Well, as we’re learning more and more about each individual patient, personalized medicine and targeted therapy, we certainly should start relying more on biomarkers. Biomarkers can be a way to select patients that would particularly fit a given treatment.

We need to lower costs. We need to make trials slicker and faster. Single-arm trials are those in which a patient just get—all the patients get the therapy. They all get the same treatment. And FDA has actually approved drugs based on single-arm trials, a much faster and efficient way to get an answer.

The problem is that the costs are going to be there. When I think about Mike and all the work that he does in developing his venetoclax (Venclexta) trial that he mentioned, Mike has put in months or years, and it’s all above and beyond his normal time. I mean his day job is to take care of patients, so all of the work that he does to develop a trial is just remarkable in the extra hours it takes and the consistency that Mike gives to doing his work. We need to make the trials more efficient.

We need to use biomarkers. We need to make them shorter. We need biostatisticians to come up with ways to give us an answer without having to approve so many hundreds or thousands of patients to all these potential new treatments.

Andrew Schorr:

So, Mike, let’s talk about that. And, Mike, first of all, I want to thank you for your—well, both of you, but, Mike, certainly in the clinic, thanks for your devotion to this.

But continuing on that, so this was brought up by Jim, biomarkers, and I know in some of the blood cancers now we’re talking about more and more minimal residual disease testing, and we’re doing genomic testing to see what genes have gone awry, what’s our version of lung cancer or a breast cancer or a myelofibrosis or whatever it is.

And then do we qualify for a trial? What’s our specific situation? Do you feel that that sort of precision medicine testing and analysis can help refine this, so we know which trial is right for which person at which time and also some analysis along the way of how is it going?

Dr. Thompson:

Yeah, so at my site I’m the director for precision medicine, and I gave a talk at ASCO on precision medicine and barriers in the community setting, so I’m very passionate about that. And I think that is one of the ways you can try to get things done with smaller numbers of patients and things done faster. And part of this is alignment, right? So there’s different perspectives, a patient perspective, a payer perspective, a pharma sponsor perspective, the physician. There’s all these different perspectives, and I think it’s trying to get them all aligned and trying to get things done faster.

So, you know, there are some areas where we don’t know enough, and we can’t use biomarkers. But there are other areas where we have a biomarker, and there’s feasibility, and we can test that quickly. And if we are looking for a large effect size—here I am in jargon mode—but if you’re looking for a big, big hit, a home run, is to look for an alteration that is very specific and we think is—a drug can target. So-called targeted therapy—it’s a little bit of a misnomer.

So—and lung cancer has been one of the hottest places for this. So there’s ALK inhibitors, ROS1 inhibitors, EGFR inhibitors, and now BRAF inhibitors, HER2 targets. So lung cancer has exploded with precision medicine therapy, and the same with melanoma and BRAF. So, you know, I think even skeptics will say you don’t really need statistics if the prior therapies, nothing worked, and you give something, and 80 percent of people respond.

There are issues with precision medicines, but the main thing is not response rate but durability. And I think that’s going to be the next iteration of the NCI Match study, which is a large precision medicine study, is stop doing just these small groups of people who are showing activity, but then they relapse quickly. And I think it’s going to look at systems analysis, and how do we overcome resistance.

But one way to get at this and another different take on it is inclusion and exclusion criteria. So this has to do with access and individualizing and being patient-centric. Many of the inclusion and exclusion criteria, when somebody says, oh, I have lung cancer, oh, here’s a lung cancer trial, and they say, oh, you can’t go on the trial. And much of that is because there’s language that’s been cut and pasted from a previous trial which is not really pertinent.

So if the new drug is metabolized by the kidney, you don’t necessarily need to look at the liver studies. And we did a small study or I was aware of a small study done by Kaiser where if we improve the inclusion-exclusion criteria, accrual rate can go up 30 percent—so no cost to that.

Andrew Schorr:

Wow.

Dr. Thompson:

And Ed Kim led a publication about six journal articles in JCO about different aspects of inclusion-exclusion criteria including function, HIV status, age, etc.

Andrew Schorr:

Well, yeah. We had Ed Kim on the program just a week ago, as a matter of fact.

So, Jim, inclusion, exclusion, so first of all, we’re in this age where electronic medical records, it would seem that at your fingertips there could be some analysis of your record and some matching or offering of trials that could come out of an analysis of your results, genomic results. Do you have ALK or ROS or whatever, if it’s lung cancer, whatever it may be maybe JAK2 positive in myelofibrosis, what is various status for us?

And also broader inclusion criteria, and Mike was getting at that, saying some was just—excluding was just cut and pasted. And a lot of us patients would feel, well, that’s just unfair. So what’s your comment on all that, about inclusion and exclusion and analysis so we can be matched with trials more easily, can be offered to us?

Jim Omel:

Inclusion and exclusion criteria are really important parts of trials. They’re what get people into trials, they’re what keep people from being in trials. And, unfortunately, Andrew, many times the criteria are very defined, very narrowed, and drug companies especially want to do it this way to get the best effective appearance of their drug. They want to get approval. And yet in the real world, in fact most times, patients who would not even need inclusion criteria are the very patients that are going to be taking these drugs.

And Mike’s right. There’s too much cut and paste. If a trial takes a thousand patients to write a proposal or protocol, too many times researchers will just take the exclusion criteria that might have been from a previous trial and, like Mike said, cut and paste it when perhaps it’s not even necessary to have creatinine values or kidney values measured so precisely on this particular drug compared to the other one.

So those are the criteria that let people in or keep people out of trials, and they absolutely need to be widened. To make a drug more applicable to the general population we need to reflect the general population more in trials.

Andrew Schorr:

Right. Right. It’s sort of a Catch-22. So if somebody is at a drug company and they’re investing hundreds of millions of dollars maybe to develop a drug, and then that trial is languishing or taking longer to get there, somebody ought to go back and say, well, can I loosen up this criteria, get the big answer and do benefit to patients who may be very willing to be into a trial that doesn’t have all of these requirements that are not really necessary? And we get the answer and get it quicker, and help people along the way. I mean, it’s pretty obvious to me, and I hope they’re watching, folks.

So, Mike, here’s a question for you, though, and you work with people in the community setting. So we have patients who have written in and said, you know what, where I go to the cancer clinic they never mentioned trials to me, and Jim alluded to the extra time it may take for physicians and their teams is when there are trials. You have just treating people with current therapies, and then you’ve got research layered on top of that. It’s very time consuming.

But what about just awareness at the community level? What can we do about that so that wherever I go into a clinic they have a clear picture of what I’m dealing with, and if there is important research going on that relates to me I hear about it? Now, maybe they say, you’ve got to go to a university center, you’ve got to go to Milwaukee, wherever you have to go, but there’s that discussion.

Dr. Thompson:

Yeah, so with all of these, you know this has been analyzed in multiple different papers. We were on one looking at a trial log, trying to look at some of these issues, and what seems to be clear is when people are offered trials they tend to go on them at about the same rate, and that has to do—seems to be somewhat independent of socioeconomic status, race, etc., or geographic area.

So one of my colleagues, Dr. Verani, told us about—about this, about rural settings how do you get people on trial. So there are different barriers. So one is the trial, and like Jim said, if you can only do some therapy that you have to come in quite a bit for that limits the geographic area you can accrue to for most people.

There are site issues where if you don’t have enough research staff to be there enough the doctor doesn’t feel supported to spend time on it. There are physician issues where they may not care about trials, or they have too much people scheduled in clinic, they’re an hour behind, and they can’t stop to spend time on it.

Also in the community setting you may be seeing every type of cancer, and you can’t remember everything, versus at many academic settings you may only see one or a cluster of types of cancer. So if you’re seeing lung cancer all day and you have 10 trials open, you probably know those trials very well for lung cancer, because you don’t care about the CLL or myeloma trials, you only care about lung.

And then there are patient factors. So patients that are in rural Wisconsin may have different characteristics, and the reason they’re in rural areas, you know, the motivations is about, you know, going in for things and stuff like that may be different than people who have the capabilities to fly to Boston or Houston or New York, and they can do that. So all of those areas are important.

Now, one potential way to help mitigate some of those things is we have got a clinical decisions support tool, which is an IT product, which our physicians have to enter in what they’re going to do with the patient. So it could be observe, no treatment, hospice or various therapies. And when they put in the cancer and the stage it pops up with the clinical trials, the first thing that pops up. And so the physician doesn’t have to do the trial, but they have to say why they’re not doing it. And so we can track over time. It doesn’t necessarily help that individual patient, but that doctor has been aware of the trial, and we kind of get an idea of why people are not going on studies, and so that’s one way to do it.

Something we just did the last week is we had a different IT product where the NCI-matched precision study opened up five new arms with different targets for different drugs. So we looked back at the number of patients that had those targets identified within our entire system, and then we screened those to see how many people were still alive, and were their organ functions still good enough to go on these trials because of the inclusion-exclusion criteria, and we found several. So we’re now able to contact the physicians and the research staff to go back for these patients that had screened for molecular testing and now they have new options.

So I think there are IT issues that you can do systemically to try to take some of those barriers away, and then each of those points does have barriers which probably have different solutions and different ways of tackling. But one reason, you know, the accrual rate hasn’t gone up a lot is it’s not easy. It’s a complex problem, so there’s not going to be one single thing you do. There’s going to be many different ways to try to improve things, including patient education.

Andrew Schorr:

Yes, well, okay. To let’s flip that over. Jim, you and I are patients. So what do we want to say, and from your perspective?

So back at the clinic and from group has, so Mike is working on IT to identify trials and have it pop up on the screen for the doctor. Okay. Great. But we’re the ones living with the condition. What can we do so that promising research that we may learn about is available to us? We can see whether it matches up with us. Maybe we have to go down the road. Maybe we have to have a discussion with our doctor to even encourage them to have you us be in a trial. How do we make it happen, okay?

Jim Omel:

Well, of course, we all need to educate ourselves about our cancer. When I was in medicine school I had heard about myeloma, but I certainly wasn’t any expert in it. I had two patients in my practice that had myeloma. I knew sort of how to take care of them. But since I developed my myeloma, I have become my own expert. And as I lead my support group, Andrew, I make them experts. I teach this cancer to them so that they can make educated decisions.

Patients are very likely to go on the Internet, watching Patient Power. In my particular cancer, they’re going to go to the IMF and MMRF to look at myeloma trials and see what’s available. And they will take that information to their doctors, many times making their doctor aware of trials that perhaps they aren’t each advocating or aware of.

So, Mike’s right. There are many factors that keep patients from trials, but one of the things that patients really do themselves is educate themselves and perhaps even to the extent of bringing or educating their doctor about what can be available for their treatment.

Andrew Schorr:

Mike, I want to ask you about cost. So you mentioned different inclusion, exclusion, or what’s your liver function or this or that. So there is a problem where maybe certain drugs or certain aspects of a trial are covered, but then your insurance company, you know, that you have or Medicare or whatever, they say, oh, no, we don’t pay for that, but yet it’s part of the trial or it goes along.

So people have a concern about cost. I want to ask you about two aspects of cost related to testing sometimes. And then also are there programs that can assist with the logistical costs for patients as well?

Dr. Thompson:

So when I trained at Mayo Clinic and MD Anderson, and when I got—first went into practice I prided myself in not caring about cost. And then I realized you have to think about these things because you can bank—you know, we bankrupt, about 40 percent of people with cancer get bankrupted. So these are huge issues for people who want to keep their houses, that want to hand something down to their kids, and cost is huge, right? So that can either be throughout the whole course of standard treatment, or it can be trying to meet the cost of going places, trying to find clinical trials.

So the Affordable Care Act and various other national and state legislative initiatives have tried to make insurance companies pay for the standard costs in clinical trials. There are some carve-outs for smaller companies and things like that, and so this is, you know, not perfect, but in general insurance companies should pay for the standard cost of clinical trials. They should pay for standard imaging stuff too, and they try to get out of that. So it’s not a perfect world, but that should be covered. And any research-associated costs should be covered by the company. Even in some NCI trials some people disagree with what should be covered and isn’t, and it’s complicated. But in general, a patient, the research cost should be covered.

Now, that does not include travel, lodging and a lot of incidentals. So there are a variety of foundations, that could be The Leukemia & Lymphoma Society, that could be other organizations which could help with that. Individual hospitals or health systems might have ways of approaching that. And sometimes there are things you can do within the various companies. So there’s a new target called Entrek, and the company Loxo, I’ve heard will fly people who wherever there’s a site and pay for them to go on the study, which I think is amazing. That’s not true for every company and every drug being developed. But that’s one way to do it.

One of the issues that comes up with IRBs if you’re giving people money, are you coercing them? And, you know, if you’re just recovering the cost to travel, I don’t think you are, right? But those are one of the things that come up. But certainly there are lots of disparities. And just like in different countries, they don’t have access to the drugs we have as standard drugs here, and not all of these disparities are going to be fixed because we have—outside of cancer we have lots of disparities in the United States, but cost is a big issue.

And then value, which we’ve been increasingly talking about in the oncology community, which is utility over cost. And that’s more for once we’ve done the trial figuring out even if shows like it works, how do we figure out how to use it based on those characteristics?

Andrew Schorr:

Thanks. And also I wanted to mention that Mike Snyder is sending that question, answering why it cost so much. I hope that answers it.

We have—you know, some people wrote in as we were preparing for this program and they were bitter because they thought they had a spouse, let’s say, that had died in a clinical trial. And that relates to a couple of things. One is transparency. Is the data from a trial and any dangers that show up, is that reported and analyzed in public, Jim? And also what are the risks being in a trial, and what is the monitoring to try to have trials be at safe as possible. So, Jim, maybe you could talk about that from a patient perspective.

I want to make sure I know what I’m getting, I know what the risks are, and if any have come up along the way I want it to be reported, and I want to know that there’s a team looking out for me.

Jim Omel:

You have every right to expect that, Andrew. If you’re in a trial you have the right to get that knowledge if there’s new things that come up that we’ve learned about. And part of every trial as it’s being written, there has to be a data safety monitoring board. These are the experts who will do what you’ve asked be done. They will monitor the trial as it goes along. They will look for any safety issues. If there are patients who are developing liver toxicities, they will find this. They will point this out and perhaps see if the trial needs to continue or if something needs to be revised.

The presence of institutional review boards review whether trials should go forward or not. Patients who are in trials actually get very, very good medical care and medical coverage. In fact, I would maintain, Andrew, that they get better care than just standard care. They have experts that are watching them even more carefully than would be in a general routine care setting because they’re looking for these concerns and problems.

The person who mentioned the bad outcome, we can’t ever say that every trial is going to be perfect. There are going to be concerns. That’s why trials are done. But they’re relatively rare, and we do have boards and review organizations during the trial, not afterwards, but during the trial to be looking out for your benefit, Andrew, so that you’re not hurt by the trial.

Andrew Schorr:

All right. But let’s say this—and, Mike, for you. So, first of all, admittedly a lot of these trial start, and people are sick people, and they’re feeling maybe the trial is their last hope. We had a friend, Lisa Minkove, who died in the CAR-T trial for CLL not long ago. She had been very sick with CLL, so we’d hoped that it would work. It didn’t work for her, whether CLL won. And we know other people whereas the learning is going on about often powerful new medicines they didn’t benefit. Or in one case, there was a drug, venetoclax we know about, there were some deaths early on when the drug was far more powerful than was originally understood. So what do we do? I mean that’s the real world I guess of scientific study, but that’s a concern, you know, Mike, of people saying, oh, my God, I’m worried about being a guinea pig the unknowns on the subject of dangers.

Dr. Thompson:

So there are a couple of things. So whenever people say—it doesn’t come up as much recently about being a guinea pig, I say, well, guinea pigs don’t have choices, so. And so like Jim has said you can drop off a trial if you want to drop off it. But—so I think for adverse events and things that can happen, one reason to randomize people is that you do understand then if you treat someone with one thing and then another and the death rate the same in both, the drug is not causing it. That’s just the disease. And a couple years ago, there was a presentation from the group at Dana-Farber on the precision medicine program, and the issue was they were taking so long to get people evaluated that their performance status or how well they felt was good, and by the time they got through the evaluation many of them had died. Because the disease, you know, when you get to fifth, sixth, seventh-line therapy it can often progress very rapidly.

And so I think that’s one of the issues, that people can feel the drug did it, and it’s hard to know. And we get these—doctors get these things called adverse events reporting forms, and we have to try to come up with is this probably related, possibly related, and we also get these forms that say you have a patient on the study. The study is open in three countries, thousands of people on it. One person died of a heart attack, and you have no idea as the physician, well, is that the same rate as—you know they’re 70 years old. Is that the same rate as this other 70-year-old. So you need the enumerator and the denominator, and that’s what the DSMB or the Data Safety Monitoring Board is supposed to do, which is look at the data and say, is this beyond what we would expect? And they can stop the trial. They can do expanded cohorts. They can do things to try and figure that out. Now, we know from like even car companies lying about their exhaust systems that if the Data Safety Monitoring Board gets false data, well, you can’t fix that. But that’s pretty nefarious. Like that I think is not something that’s commonly happening and would be a very serious thing to happen.

Now, one thing for transparency is that almost all studies I’m aware of get registered on clinicaltrials.gov or maybe some other sites but usually that site, and they’re supposed to report out the outcomes. It’s not also a perfect process, but you should be able to see how long the study has been open, are there any complications related to it and those types of things. So this whole process is not perfect, but I would say in general the people at the companies are trying to develop something they think is going to work. They’re trying to do it safely, both to help develop their drug well as well as to avoid a bunch of regulatory issues, and the people on the Data Safety Monitoring Board are trying to do their best to answer these questions. But the smaller the number of patients which increasingly will take the trials we are doing and almost are aiming for, it’s harder to be definitive about when these things happen and what caused it.

Andrew Schorr:

Right. Right. It’s imperfect, as we said. So, Jim, Mike Thompson mentioned earlier, gave lung cancer as an example and, of course, across immunotherapy, there are so many companies endeavoring to move this research along. So let’s say you had lung cancer or one of these others where this is big, although it’s going on in the hematology area too, so a patient says, oh, my god, there are all these trials, and I might qualify for one, two, three, four. How do I prioritize? What do I bet on? And maybe my own doctor is doing more than one. So what do you say to patients if they become receptive to being in a trial and there’s more than one trial that they qualify for?

Jim Omel:

That’s a very good question, and it’s a nice kind of problem to have, to have choices of trials. I think, Andrew, the best answer is the patient needs to look at what they are looking for. Are they looking for longevity? Are they looking for something that’s going to expend their life? Are they looking for a trial that maybe will greatly improve their quality of life? Perhaps they’re looking for a trial that gives them one pill per week versus two injections a week. So there are certainly effectiveness end points. There are different things that patients find of value.

But to answer your question it really comes down to each patient needs to ask themselves, what is it I’m looking for in a trial? Do I want something that makes my burden lighter? Do I want something that’s going to extend my life? How much am I willing it accept as far as potential problems versus the standard of care that I know what the problems exist with if I don’t go on a trial?

Andrew Schorr:

Right. So that’s a question we got in, is they’re trying to assess that. One was about how do I prioritize? The other is, by being in a trial, Mike, is it going to make me sicker? Like, to do I have to go through the valley of the shadow of death to get, hopefully, to a better place, and how do you discuss that with your doctor when not everything is known?

Dr. Thompson:

Yeah, maybe I’ll kind of step back and say for phases of trials, Phase I, the intent—both ASCO and NCI say the intent of a Phase I trial is therapeutic. But the statistical design is to evaluate safety. A Phase II is to look at initial efficacy or how well it works, and Phase III is to compare versus standard of care the efficacy. So there’s other types of designs, phase 0, Phase IV and other things, but it used to be, I think, you know, I—we would say don’t go on a Phase I unless that’s the last option because you’ve already gone through the safety initial efficacy if it’s a Phase III trial. It costs a lot of money to do Phase III trials so fewer are being done now, and we’re kind of finding that in this era of precision medicine people are going on trials, and there’s no one rule, but I look at it as if it’s a study involving a lot of different groups of patients, a lot of—you know, it’s not individualized to you, I don’t know, but I think it will have less of a benefit probably than if it’s something like a study designed for BRAF melanoma back when that was a study and you have BRAF. Well, it’s targeted for you. It doesn’t mean it will work, but even if it’s an early phase, a Phase I or II trial, it’s really aimed at your disease.

And we’re finding this with venetoclax, with T1114, and there’s other markers, FLT3 in AML, all these things, and sometimes we find that the drug doesn’t work like we think it’s going to work. The ALK and ROS story in lung cancer, it may benefit other people that we didn’t recognize before, and that’s part of–we’re trying to find people besides T1114 that respond to venetoclax in myeloma because it looks like some people will. But I think as we’re getting more targeted therapy it doesn’t mean there’s no toxicity, but it at least has the suggestion that we’re targeted more at your specific cancer. And some of these pills can have as much toxicity as IV chemo s, but our aim is to decrease toxicity and increase efficacy. And I think, like Jim said, you’ve got to look at different trials and hopefully with a physician who has time to sit down and run through several scenarios. And some people will take the most aggressive therapy because that’s what they’re after, and some people will try something that’s easier and closer to home. So everyone’s values are a little bit different, and you have to try to individualize as a patients.

Andrew Schorr:

Right.

Dr. Thompson:

One thing about trial matching is besides clinicaltrials.gov, there’s myeloma and other groups that are doing these matching, so you can put in characteristics of your cancer and you can try to filter out and get a closer approximation, including at clinicaltrials.gov you can click on the states in the surrounding area or how many miles you’re willing to travel.

Andrew Schorr:

Right. I would mention, put in a plug for our advocacy group friends, whether it’s Lung Cancer Alliance, Bonnie Addaria Lung Cancer or the International Myeloma Foundation with The Leukemia & Lymphoma Society, you can be in contact with them directly and talk about your situation, and they will often be very aware of trials and how it’s starting to line up with these sub groups, subtypes of illness. Here’s a question we got it in with Jack. I just want to get in a couple more before we have to go. This relates to what you were talking about the National Cancer Institute’s Match trial, as I understand it, Mike. He said, regarding precision medicine I thought I heard that initial results have been disappointing for the NCI trial which treats patients with a specific mutation with a specific drug for that mutation. How does this impact precision medicine? You want to talk on that? Mike?

Dr. Thompson:

Yeah, so the people who are opponents of precision medicine would say that the SHIVA trial in Europe and the NCI Match trials were failures. I think you need to look at it a little more carefully. And if you do a huge screening and you don’t have many drugs you don’t have many matches and not many people are going to benefit. So there are some arms in match that match the accrued the number they wanted, and the drugs didn’t work well. So those were truly we think negative studies. But I think the things about Match are there is a huge interest in the community, and they had thousands or several hundred people screened when they only had a few arms opened, and those people weren’t matches, and it basically overwhelmed the system. And then they had to rejigger it to open up more arms. So I think we could—you know, pick holes in the design of the initial study, but I think it took everyone by surprise how much interest there was in trying to personalize these molecular therapies. And other iterations such as ASCO TAPUR, there’s company versions of it like Novartis Signature, and I think the new design of Match do allow for better match rates, and we’ll see how after they’ve adjusted how well they can hit their targets.

Andrew Schorr:

Okay. So that’s an example, where we’re going through a makeover there. Before we go, Jim, we have people watching from all over the world, and Mike alluded to sometimes trials done in other countries. Certainly they are. So we have somebody from New Zealand, we have people from other countries now. How do I access trials? Does it have to be in my country? Or what would you say to an international audience as far as finding out what’s available to them?

Jim Omel:

That’s a difficult question because every country has their own standards. Each country has their own boards that review. What is allowed in some countries are not even allowed. Observational trials can have more importance in some countries than others. Again, it’s a tough question. I think perhaps the person who asked it really needs to be again their own advocate and go online, go with their physician, go to their local support groups, go to their national groups, because they’re the ones that can give that local person their answer. There’s no one set answer for every country because there are some many variances.

Andrew Schorr:

Right. I do want to tell one of my favorite stories. I had a friend Jan Rin in Dublin, Ireland. She had a tremendous problem with more advanced chronic lymphocytic leukemia, one of the conditions I have, no trial for her there. She heard about Imbruvica being studied in Leeds, England, different health system, national health system. She was in Ireland, didn’t have it. She got permission from the Irish government to go over to Leeds and be in Dr. Hellmann’s trial there, and I think it saved her life. She would tell you that. So she had to be pushy. There were newspaper articles. She had to do lots of things to make it happen. It’s going to be varied by country but it starts with…

Jim Omel:

…drug like the one you mention, and it’s not available in the country, and there’s so much of that in myeloma. We have many, many drugs in the US that they don’t have in other parts of the world, and it would be so sad to be a patient in those countries, know that a treatment like that is available but not have access to it. So we all need to work to get these drugs available to patients wherever they’re at.

Andrew Schorr:

Right. Amen. I want to just get some final comments from you. We may just go a couple minutes over. So, Mike, the process is improving, I hope, you’re working on it. Can we feel confident that these gaps, if you will, improving it for prevision medicine, more awareness among the doctors wherever we may go, financial assistance, working with the insurance companies, are you working on it so that this process, we can have some improvement and hopefully have higher levels of enrollment and can get drugs approved quicker?

Dr. Thompson:

Yeah, I think we’re all very concerned about it. We should all be aligned in having more patients on trial, moving things faster and getting it done more cheaply. And I think we’re making progress. It’s not as fast as any of us want, but we’re all trying to move the ball forward.

Andrew Schorr:

Okay. So, Mike, it comes—excuse me. Jim, it comes down to us then as patients. We have to push, right? We have to see what’s within ourselves, what are we willing to do, understand our clinical situation and what’s going on for our cancer, and we’ve got to push, right?

Jim Omel:

And one of the things we need to push for are more interesting trials. We need to make pharma companies put up their drug against another pharma company’s drug. I think it’s so troubling when they’re afraid to take big steps. They just take little, incremental steps with their trials. If we can put drug A of one company versus drug A of another company—pharma companies are really reluctant to do those kinds went trials, and yet those are the kind that would be exciting to patients. I could give certain names of myeloma drugs, but we won’t get into that. It just needs—we need to get better, more interesting trials, and that will attract patients.

Andrew Schorr:

Okay. So I want to just put in a plug for something. We started something at Patient Power called the Patient Power Ambassador Program, and you can see it listed on our site, where you can share your voice. So we can all work with Jim, work with Dr. Thompson, and we cannot just be getting what’s right for us, but we can push on this process. So please consider doing that. Because I want to thank you, Jim Omel, for not just getting what’s right for you as a myeloma patient, but working on these government panels and with advocacy groups to try to advance it for all of us. Jim Omel, thank you for doing this.

Jim Omel:

Thank you, Andrew. It’s a pleasure to do this, and I’ll keep doing it.

Andrew Schorr:

Yes. And long life, Jim. Thank you.

Jim Omel:

Thank you.

Andrew Schorr:

And, Dr. Mike Thompson, thank you, Mike, for your leadership too and those extra hours put in, not just for programs like this but all the clinical research speaking to industry and the government to try to improve this process. Thanks for being with us, Dr. Mike Thompson.

Dr. Thompson:

Thanks for having me on, and I think this is the some of the most powerful patient educational material that people can get, this type of program.

Andrew Schorr:

All right. Thank you so much. So, folks, we’re all in this together. So you have your own issues about whether you know about trials, whether you want to be in a trial, that’s right for you or a loved one, whether it’s close to home, not close to home, so—but we have these discussions. So please look ongoing at the clinical trials mythbuster series. The let us know how we did today. You can always write to me, andrew@patientpower. Our producer, Tamara, T-A-M-A-R-A, at patientpower.info. And talk to your own doctor and your own healthcare team about clinical trials and where they line up, what are the obstacles, for you participating. And let’s see if we can improve this process and ultimately have more medicine that can lead to a cure for us be available sooner. Thank you for watching. We’ve done our best today, but this is an ongoing discussion. In Carlsbad, California, I’m Andrew Schorr. Jim joined us from Nebraska, Dr. Mike Thompson joined us from Wisconsin. Worldwide, we’re here for you. Remember, knowledge can be the best medicine of all. 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.


Please remember the opinions expressed on Patient Empowerment Network 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.