Tag Archive for: PET Scan

How Are Patients on Myeloma Maintenance Therapy Monitored?

How Are Patients on Myeloma Maintenance Therapy Monitored? from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Omar Nadeem explains how a follow-up care and monitoring plan for patients on maintenance therapy is determined.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

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How Is Relapsed or Refractory Myeloma Managed?


Transcript:

Katherine Banwell:

Dr. Nadeem, many patients are on maintenance therapy following active treatment. So, how is a patient on maintenance therapy monitored? 

Dr. Omar Nadeem:

Yes, so, majority of the time just with blood work. We don’t necessarily need to do a lot of bone marrow biopsies and PET scans for a majority of patients that are on maintenance therapy unless we’re either worried about their blood markers or some symptoms. Generally speaking, any time – it depends on what maintenance therapy they’re on, of course. If they’re just on lenalidomide (Revlimid), which is the most commonly used maintenance therapy, a lot of times we check in with them every one to three months. 

Depending on how their disease status is and how they’ve been doing and whether there’s any side effects that we need to worry about. So, they still have to see their doctors, still have to get the blood work. Usually you can get away with having it done no more than once a month or so, unless they are on other medications along with Revlimid, where we then have to check in with them a little bit more frequently. 

And some of that changes, so patients can be on maintenance therapy for five plus years, and we get a very good sense of how they are doing and kind of how their disease is doing, and we can kind of be a moving target in terms of the frequency of the follow-ups. 

What Are Currently Available Myeloma Treatments?

What Are Currently Available Myeloma Treatments? from Patient Empowerment Network on Vimeo.

Dr. Omar Nadeem reviews myeloma treatment classes, including immunomodulatory therapies, proteasome inhibitors, and monoclonal antibodies. Dr. Nadeem also discusses how combining these therapies has boosted the effectiveness of myeloma treatment.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

See More From INSIST! Myeloma

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Understanding Personalized Medicine for Myeloma

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How Is Research Advancing Myeloma Treatment and Care?


Transcript:

Katherine Banwell:

Dr. Nadeem, what types of myeloma treatment classes are currently available?  

Dr. Omar Nadeem:

Yes. So, we started over three decades ago plus with just having basically steroid medications and some older chemotherapy drugs that weren’t very targeted at all, and that was basically all we had up until about a little over 20 years ago, where immunomodulatory drugs were first discovered to be effective in multiple myeloma, and that included thalidomide (Contergan or Thalomid) and now a commonly used agent called lenalidomide, or Revlimid.  

After that, we had a next class of medications approved called proteasome inhibitors that work differently than the immunomodulatory drugs, and then we combined all of these therapies about a decade plus ago and showed that that was better than anything else that we were doing before that. So, combining the steroids with the immunomodulatory drugs and proteasome inhibitors became the standard of care. 

And then we had the next class of drugs approved in 2015 called monoclonal antibodies, and that’s the first time we have monoclonal antibodies approved for myeloma, and it first started in patients that had relapsed myeloma, and then they made it all the way up to front line therapy with a drug in particular called daratumumab (Darzalex).  

And now what we’re going is entering an era of combining all four of these therapies, just like we did 10 years ago with three drugs, and showing that combining four drugs is actually better than three. And the important thing there is that it’s not necessarily adding cumulative toxicity. These are targeted therapies; they all work differently, but they all work really well together. So, now combining these agents has allowed us to really treat the disease effectively and allow for patients to tolerate the therapies.  

And then over the last couple of years, we’ve now entered kind of the next renaissance in myeloma where you have immunotherapies, and these are sort of true immunotherapies, in some cases taking the patient’s own T cells and then genetically modifying them to recognize myeloma cells and putting them back into patients. This is called CAR T-cell therapy, and that’s now approved for patients with multiple myeloma.  

And that again, just like the previous drug, sits in patients that have – you know, at a space where patients have had multiple relapses. But we’re now studying that earlier and earlier, and that along with another class of drugs called bispecific antibodies that also use your T cells via a different mechanism. A lot of exciting things going on, and we keep adding to the available agents for this disease.  

Understanding Personalized Medicine for Myeloma

Understanding Personalized Medicine for Myeloma from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Omar Nadeem and Dr. Betsy O’Donnell discuss the personalized approach to treating myeloma and the factors that are considered when making care decisions.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

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Transcript:

Katherine Banwell:

Dr. Nadeem, as we begin our treatment discussion, would you define personalized medicine as it relates to myeloma care? 

Dr. Omar Nadeem:

Yes. I think we’re getting better and better at really having a personalized treatment plan for each individual patient with multiple myeloma. I think Dr. O’Donnell defined before, we are identifying some of the markers where we have targeted therapy for, and we hope with time we’ll discover more and more targets that can truly lead to personalized medicine for individual patients. 

Right now, though, we have a lot of approved therapies for multiple myeloma, and that list is getting longer and longer basically every month, it seems, nowadays. So, when we have so many tools in our toolkit, we then have to figure out, well, which strategy works for which patient? And the fact that we have effective therapies, we’re able to tailor how much of one particular therapy a patient may benefit from. So, some of the decisions that come into play is which medication should I combine for this patient which will lead to obviously disease eradication? 

And then also, how much do I need to intensify that treatment? Do we need to think about doing a stem cell transplant or not? Yes or no?  

There are lot of pros and cons, right? So, it’s a very personalized decision that we have, looking at the disease factors, but also a lot of personal factors because transplant interrupts life, and then we have to make sure that that fits with that particular patient’s lifestyle.  

And then we talk about maintenance therapy. You know, that’s the therapy that is designed to kind of keep the disease away usually for many, many years for the majority of patients.   

But what does that look like, right? Does that include just pills? Is it going to be shots plus pills? Is it going to be a combination, etcetera? So, we have all the discussions at each phase of myeloma, and we discuss with them about what the pros and cons are and how that may fit into their particular lifestyle. 

Katherine Banwell:

Dr. O’Donnell, what factors do you consider when choosing a treatment approach? 

Dr. Betsy O’Donnell:

So, I think you’ve heard from all of us that we really try to have an individualized approach. When we’re talking about multiple myeloma, one of the main factors that I think about is really kind of the overall wellness of the patient. Historically, we had different categories of transplant eligible, transplant ineligible. 

And so that can influence some of the decisions. Really it comes down to what is it the person’s performance does? How well are they doing in their day-to-day life? And that really can dictate the intensity of the therapy. We know that age is just a number, it really is, so there are factors beyond that. What other medical problems do people have? What are the specifics of how well their kidneys are working? 

And so the biggest thing that we can work with is the dose. In fact, we’ve had work that shows that using lower doses from the get-go in older patients allows almost identical outcomes, but really gives patients a tailored dose to where they are at that juncture in their life.  

And so remember, myeloma is much more like a marathon, and so you have to set out at a pace that can be sustained. We treat people continuously. There’s an induction phase where we use a multiple drug combination, but beyond that, as Dr. Nadeem just said, they go on to maintenance, and that maintenance is indefinite. And so you have to set out at a pace or at a dose that you can sustain. 

Different medications have different toxicity profiles, so if someone had, let’s say, cardiac or heart issues, we might steer away from some medications that may exacerbate those. So, every decision is individualized. It’s based on who the patient is, where they are in their life, what other medical problems they have, and what we think they will do best with over time, not just in a short timeframe. 

How Is MGUS Monitored?

How Is MGUS Monitored? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Irene Ghobrial discusses how patients with monoclonal gammopathy of undetermined significance (MGUS) are monitored over time and shares an update on research being conducted to learn more about this myeloma precursor condition.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Learn more about Dr. Ghobrial.

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Transcript:

Katherine Banwell:

Dr. Ghobrial, how are people with MGUS monitored? 

Dr. Irene Ghobrial:

Yes, so how do we even diagnose them, right? It’s a big question because it’s incidentally found. Someone will go to their primary care doctor and have a little bit of a high protein or slight anemia, and it may not be related, and then their doctor will check for serum protein electrophoresis, and that’s pure luck. We want to take away luck from this equation. We want to take away chance from this equation. 

And we want to start screening people who are at risk, and we are doing that with the PROMISE study. It’s online available to everyone nationwide, international now, where you can sign up on promisestudy.org and try to ask the question that we do for you research level, the serum protein electrophoresis, and a new test called mass spectrometry that is much more sensitive than SPEP to find it. 

Now, once we find MGUS, we want to know what is my own personal risk of progressing to myeloma? Because I could be 30 years old with MGUS, and likely I will progress to myeloma in the next 10 years, 20 years, and by the time I’m age 60, I would have been diagnosed with myeloma. Just a true case in many, many people. If people are diagnosed today with myeloma, they are going to their doctor because they had back pain or anemia, and they are diagnosed with myeloma. In almost all of the cases, they would have had MGUS and smoldering, but they didn’t know about it three years ago, four years ago because they never got tested for it. 

So, we want to change that completely and become proactive rather than being reactive and waiting for symptoms to happen. Once you have MGUS or smoldering, because we don’t know, we start looking for all of the things to help us identify your risk of progression. So, we look at the height of your M-spike. Is it small or big? And then we in many cases say okay, maybe you need a bone marrow biopsy if your M-spike is a little bit on the higher side because we don’t want to miss smoldering myeloma, which will change the prognosis. 

And then we start looking at do you have anemia? Do you have kidney failure? Do you have any of the other things that may predict that you may be actually going into myeloma? 

We also look at it more as a movie rather than as a snapshot, rather than a picture. If your M-spike is changing or your light chain is changing every three months, every six months, that’s an indicator that the cancer cells are doing something. They’re working in there and growing, and that’s why they’re increasing the M-spike and the light chain. 

And that evolving number is actually a very big predictor of telling us that there is a risk of progressing. Those are all clinical markers that we can do. When we look at the FISH, which we talked about, we can tell the certain markers are chromosomal changes that tell you that those cancer cells want to grow a little bit faster. So, 1q abnormality, 4;14, 14;16, 17p, all of those have been shown that when you have them, the cancer cells are not just sitting around and doing nothing. They’re actually starting to grow, and we want to catch them and understand what is the biology of the disease rather than just how many cancer cells you have. 

We do a lot of research level, and potentially now we’re going to give them back to the patients as clinical level, where we can give you more information about that prediction of your risk of progression. One of my colleagues calls it predicting the hurricane. We know that the hurricane will happen, and it’s a question of how precise could you be? We’re the Weather Channel men here.  

And we could be very precise and tell you it’s going to hit Miami at 2:00 in the afternoon tomorrow, and you could be prepared for it and get out of there. Or, you could be completely unprepared because we were not very accurate in our prediction and tell you it may hit the whole East Coast in the next two weeks. That’s not accuracy. So, we want to be more accurate in our prediction of myeloma because one person will never develop myeloma and can go have fun and enjoy life and not be worried and anxious about their risk, and another person we might say let’s watch you more carefully, or let’s think of interception preventing things. 

So, we do things called next-generation sequencing, taking all of those small numbers of cancer cells, even as little as single cells, and we can do whole genome sequencing and give back that information.  

We look at the immune cells and give back that information. We can do mass spectrometry. And with Betsy and Omar, we’re doing more and more tests so that when we have this prediction model, circulating tumor cells and so on, we can be more accurate in giving you that prediction. 

And help you make the next decision of are we watching carefully, are we preventing and intervening with behavior modification with other things? Are we intervening with therapy to intercept the disease? 

Katherine Banwell:

When are more in-depth tests necessary?  

Dr. Irene Ghobrial:

It depends, of course, on everything. I would probably say for every patient, it is a unique discussion. Some patients will tell me, “Let’s watch again in three to six months, and then I will do more testing,” and some patients want to know everything immediately. And we have those discussions with every patient, and we tailor our therapy as well as our diagnostics workup with every patient, depending on how much they want to know, how much their risk is, and how much they want to be involved in that discussion of how much to prevent myeloma. 

What Should Patients Know About Myeloma Testing?

What Should Patients Know About Myeloma Testing? from Patient Empowerment Network on Vimeo.

Testing following a myeloma diagnosis, or relapse, can impact care and treatment decisions. Drs. Betsy O’Donnell and Omar Nadeem provide an overview of essential myeloma testing, how the test results impact staging, and discuss recent advances in testing that have changed myeloma care.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

See More From INSIST! Myeloma

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Transcript:

Katherine Banwell:

Dr. O’Donnell, let’s move on to testing. What tests are necessary to help understand a patient’s specific disease? 

Dr. Betsy O’Donnell:

Absolutely. So, testing really does depend a little bit on the stage at which your disease is found. In general, we use a very specific blood test that lets us know that there is clonal protein present. Remember, plasma cells are a type of white blood cell, and they make something called antibodies. We use a test called a serum protein electrophoresis, which is a blood test – an SPEP, we call it – that can tell us the difference between normal, healthy antibody and clone that are made from the plasma cells that we see in MGUS, smoldering, and multiple myeloma. 

So, that’s a very important test, and sometimes your primary care doctor may notice that your total protein is elevated and send that test. 

Or there may be other things that tip them off. Perhaps the kidneys are not where they used to be. And so that test is sent, and that’s the first tip-off that someone might have a plasma cell disorder.  

Once we identify that there’s a plasma cell disorder, then that can set in place a workup, depending on the amount of clonal, monoclonal, M-protein that we see. So, sometimes that involves bone imaging. Historically that was a skeletal survey where we took lots of X-rays of your body. Now we have other tests we use. PET scans, CT scans, whole body MRIs. Sometimes it depends where you’re getting your treatment, and also it depends a little bit on your doctor’s degree of suspicion.  

Bone marrow biopsies are a procedure that we sometimes do. We use a thin, hollow needle to take out just a little piece of bone, about the size of an inchworm, and take some fluid with it. There’s actually fluid inside the bone marrow.  

And that can tell us, just as Dr. Ghobrial was defining the spectrum of plasma cell disorders, based on the percent of plasma cells, that can tell us where somebody belongs, which group they might belong in. So, we can use all of these tests to help give us a good sense of how much disease someone has and where in the spectrum or continuum a person is – MGUS, smoldering, or multiple myeloma. 

Katherine Banwell:

Okay, great. Thank you. I’m assuming these tests can help with understanding the stage of a patient’s myeloma. So, Dr. Nadeem, how is myeloma staged? 

Dr. Omar Nadeem:

Yes. So, myeloma is staged very differently than traditional cancers. Because this is a blood disease, we don’t really think about it like we may in other solid tumor cancers, where if it’s spread to multiple locations it’s IV, etcetera. That doesn’t apply to multiple myeloma. It’s actually staged out of three stages, and uses your blood work for the most part, some blood tests, to help identify which stage you are. Historically, that has correlated with how you may do. 

However, now we are learning that it’s far more to this story than just the blood work. So, we’re now using our bone marrow test results, particularly a test called a FISH test, which looks at the mutations that are present in examinable plasma cells, and if you have presence of some of these high-risk markers, that can actually either upstage you or downstage you if you don’t.  

So, we’re now I think becoming a little bit smarter how we think about this disease. It’s not just based on some blood test. We’re actually looking at the biology of some of these cells and the amount in the bone marrow. A lot of times patients ask, “Well, if I have 50 percent, 60 percent, or 80 percent involvement of the bone marrow, that actually does not have anything to do with staging, right?” So, I think it’s important to know that it’s actually a very unique staging system in multiple myeloma.  

Katherine Banwell:

Okay. Dr. O’Donnell, the landscape of myeloma has changed significantly in recent years. How have advances in testing changed care from myeloma patients?

Dr. Betsy O’Donnell:

So, I mean, the landscape has changed incredibly just in terms of the treatments we have, and I think that Dr. Nadeem was talking about something really important. 

In that when we look at FISH, which allows us to know the biology a little bit more, sometimes it helps us to decide kind of the risk that a patient is. We aren’t really at the point now where we do truly tailored therapies, like you see in some cancers, where we can detect specific mutations and pick drugs that align with that, but there are some that we do use. An example would be a drug called venetoclax (Venclexta), which works very well in patients who have a specific translocation, 11;14. 

So, there is some degree in which we use that FISH and those cytogenetics to help define our treatments, but also really we’re just fortunate that we have new and evolving therapies. We’ve changed how we treat myeloma in the up-front setting, and then at the back end we have an exploding field of immunotherapies, CAR-T cells, bispecific antibody that we’re now using that really have tremendously benefited our patients.  

Katherine Banwell:

Dr. O’Donnell, should all patients undergo in-depth testing, like cytogenetics?  

Dr. Betsy O’Donnell:

Yes, so if you’re doing a bone marrow biopsy, absolutely. The question in terms of who needs bone marrow biopsies, if someone has a low risk MGUS, those patients don’t necessarily require a bone marrow biopsy. It’s an invasive procedure, it’s an uncomfortable procedure. But if we’re doing a workup for multiple myeloma or smoldering myeloma that includes a bone marrow biopsy, then absolutely. 

Katherine Banwell:

Okay. Dr. Nadeem, what are you looking for with cytogenetics, and how might test results affect prognosis and treatment? 

Dr. Omar Nadeem:

Yes, so as mentioned earlier, there are some mutations that are considered high risk, I will say with the caveat that we don’t fully understand every single mutation yet or have identified every single mutation yet that may be high risk or low risk.  

But there are roughly five that we have identified that if a patient has one or two or several of those abnormalities, then their disease may behave a little bit more aggressively or may not respond as well to treatment. 

However, I think myeloma is just very complicated, so we look at a lot of these results in the beginning, both whether they may be good or bad. But I think, ultimately, we have to see how patients do, and that by far is the most important prognostic factor, in my opinion. So, if we look at some of these tools, including staging, some of the bone marrow results and cytogenetics, and try to give some prediction in terms of what we may see from this person’s disease, but ultimately the treatments that are so effective now really dictate the course for the majority of the patients. 

Katherine Banwell:

Are there specific tests that patients should ask for that could impact their care decisions? 

Dr. Omar Nadeem:

Yes, I think it depends on where they are in their disease state. So, if we’re looking at whether a patient has a precursor or plasma cell disorder or multiple myeloma, then they need all the testing to help us figure that out. 

So, that includes a bone marrow biopsy, the FISH testing as we just talked about. Advanced imaging like a PET scan or an MRI is now critical to identify patients that may have multiple myeloma versus those that have a precursor condition. So, we used to count on X-rays, as Dr. O’Donnell mentioned, but now really we do prefer one of those advanced imaging techniques for patients to undergo so that we can know. 

So, I think if they have basically those tests completed, that gives us most of the information that we need. 

Expert Advice for Navigating Myeloma Treatment and Care Decisions

Expert Advice for Navigating Myeloma Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Irene Ghobrial, Dr. Omar Nadeem, and Dr. Betsy O’Donnell, review essential testing that may impact the prognosis, care, and treatment options for patients with myeloma. The experts also discuss additional factors that are taken into consideration when choosing a therapy and share updates on new and developing myeloma research.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Learn more about Dr. Ghobrial.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

See More From INSIST! Myeloma

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Transcript:

Katherine Banwell: Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to hear perspectives from three myeloma experts on how to access personalized care for your myeloma. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Well, let’s meet today’s guests. I’ll start with Dr. Irene Ghobrial. Dr. Ghobrial, welcome. Would you please introduce yourself? 

Dr. Irene Ghobrial:

Absolutely, and thank you for having us. My name is Irene Ghobrial. I am a professor of medicine at Dana-Farber Cancer Institute in Boston.  

Katherine Banwell:

Thank you. Also with us today is Dr. Omar Nadeem. Thank you for being with us. Would you introduce yourself? 

Dr. Omar Nadeem:

Hi, everyone. Thank you for having me. My name is Omar Nadeem. I’m an instructor in medicine at Harvard Medical School and I work with the faculty at Dana-Farber myeloma program. 

Katherine Banwell:

Okay, lovely, thank you. And last but not least is Dr. Betsy O’Donnell. Thank you for joining us today. Would you introduce yourself to the audience? 

Dr. Betsy O’Donnell:

Sure, and thank you for having us this morning. My name is Betsy O’Donnell. I’m an assistant professor of medicine at the Dana-Farber Cancer Institute specializing in plasma cell disorders. 

Katherine Banwell:

All right. Thank you to all of you for taking the time out of your schedule to join us today. Before we delve into our discussion, let’s start with understanding the types of myeloma. Dr. Ghobrial, what is MGUS? 

Dr. Irene Ghobrial:

So MGUS, or monoclonal gammopathy of undetermined significance, is a precursor or the stage before myeloma happens, and it’s actually a very common disease or entity in many, many of us as we get older. In fact, maybe 5 percent of the population over the age of 50 would have this early MGUS. 

It doesn’t mean that it’s cancer. It’s a precursor to cancer, and we can talk more about it as we go on. 

Katherine Banwell:

All right. Is it the same as smoldering myeloma, or is that something different? 

Dr. Irene Ghobrial:

It’s not. It’s an earlier stage than smoldering myeloma, and it’s hard to actually make the right definitions. But currently what we say is if you have more than 10 percent cancer cells or plasma cells in your bone marrow, then it’s smoldering myeloma. And by the name, smoldering, it’s almost myeloma. It’s ready to go on fire, but it’s not there yet.  

MGUS is before that, and the difference is that the chance of progression from MGUS to myeloma is only 1 percent per year, so many, many people will never progress to myeloma. While smoldering myeloma, just because there are more cancer cells in the bone marrow, has a higher chance of progressing, which is 10 percent per year. And in some people, a very high chance of progression of 50 percent in two years. 

And we want to make sure that we catch those cases early and not wait for myeloma to happen. 

Katherine Banwell:

How would you define myeloma? 

Dr. Irene Ghobrial:

So, myeloma is currently defined as the same thing. The number of plasma cells in the bone marrow could be above 10 percent or more, or you have a protein in the blood. But the problem is that you’ve already had problems. You’ve had symptoms of end organ damage, so we have either high calcium, bone lesions, or bone fractures, anemia, kidney failure.  

And then now or more recently, we added a few more things to tell us these people are going to really develop myeloma soon. So, it used to be part of smoldering myeloma, now it’s part of the definition of myeloma, so that we can treat patients earlier, which is if your light chain level is very high, above 100 for a ratio, or if you have multiple lesions by something called an MRI or a PET CT scan instead of the traditional X-rays, or if your bone marrow has a lot of the plasma cells, more than 60 percent. 

And these were new definitions to make sure we don’t wait too much until people have an organ damage or symptoms and then we treat them. And you’ll hear from us that we think we should be treating people even earlier than that.  

Katherine Banwell:

Well, thank you for that. That’s very helpful. Dr. O’Donnell, let’s move on to testing. What tests are necessary to help understand a patient’s specific disease? 

Dr. Betsy O’Donnell:

Absolutely. So, testing really does depend a little bit on the stage at which your disease is found. In general, we use a very specific blood test that lets us know that there is clonal protein present. Remember, plasma cells are a type of white blood cell, and they make something called antibodies. We use a test called a serum protein electrophoresis, which is a blood test – an SPEP, we call it – that can tell us the difference between normal, healthy antibody and clone that are made from the plasma cells that we see in MGUS, smoldering, and multiple myeloma. 

So, that’s a very important test, and sometimes your primary care doctor may notice that your total protein is elevated and send that test. 

Or there may be other things that tip them off. Perhaps the kidneys are not where they used to be. And so that test is sent, and that’s the first tip-off that someone might have a plasma cell disorder.  

Once we identify that there’s a plasma cell disorder, then that can set in place a workup, depending on the amount of clonal, monoclonal, M-protein that we see. So, sometimes that involves bone imaging. Historically that was a skeletal survey where we took lots of X-rays of your body. Now we have other tests we use. PET scans, CT scans, whole body MRIs. Sometimes it depends where you’re getting your treatment, and also it depends a little bit on your doctor’s degree of suspicion. 

Bone marrow biopsies are a procedure that we sometimes do. We use a thin, hollow needle to take out just a little piece of bone, about the size of an inchworm, and take some fluid with it. There’s actually fluid inside the bone marrow.  

And that can tell us, just as Dr. Ghobrial was defining the spectrum of plasma cell disorders, based on the percent of plasma cells, that can tell us where somebody belongs, which group they might belong in. So, we can use all of these tests to help give us a good sense of how much disease someone has and where in the spectrum or continuum a person is – MGUS, smoldering, or multiple myeloma. 

Katherine Banwell: Okay, great. Thank you. I’m assuming these tests can help with understanding the stage of a patient’s myeloma. So, Dr. Nadeem, how is myeloma staged? 

Dr. Omar Nadeem: Yes. So, myeloma is staged very differently than traditional cancers. Because this is a blood disease, we don’t really think about it like we may in other solid tumor cancers, where if it’s spread to multiple locations it’s four, etcetera. That doesn’t apply to multiple myeloma. It’s actually staged out of three stages, and uses your blood work for the most part, some blood tests, to help identify which stage you are. Historically, that has correlated with how you may do. 

However, now we are learning that it’s far more to this story than just the bloodwork. So, we’re now using our bone marrow test results, particularly a test called a FISH test, which looks at the mutations that are present in examinable plasma cells, and if you have presence of some of these high-risk markers, that can actually either upstage you or downstage you if you don’t.   

So, we’re now I think becoming a little bit smarter how we think about this disease. It’s not just based on some blood test. We’re actually looking at the biology of some of these cells and the amount in the bone marrow. A lot of times patients ask, well, if I have 50 percent, 60 percent, or 80 percent involvement of the bone marrow, that actually does not have anything to do with staging, right? So, I think it’s important to know that it’s actually a very unique staging system in multiple myeloma. 

Katherine Banwell:

Okay. Dr. O’Donnell, the landscape of myeloma has changed significantly in recent years. How have advances in testing changed care from myeloma patients? 

Dr. Betsy O’Donnell:

So, I mean, the landscape has changed incredibly just in terms of the treatments we have, and I think that Dr. Nadeem was talking about something really important.  

In that when we look at FISH, which allows us to know the biology a little bit more, sometimes it helps us to decide kind of the risk that a patient is. We aren’t really at the point now where we do truly tailored therapies, like you see in some cancers, where we can detect specific mutations and pick drugs that align with that, but there are some that we do use. An example would be a drug called venetoclax (Venclexta), which works very well in patients who have a specific translocation, 11;14.  

So, there is some degree in which we use that FISH and those cytogenetics to help define our treatments, but also really we’re just fortunate that we have new and evolving therapies. We’ve changed how we treat myeloma in the up-front setting, and then at the back end we have an exploding field of immunotherapies, CAR-T cells, bispecific antibody that we’re now using that really have tremendously benefited our patients.  

Katherine Banwell:

Dr. O’Donnell, should all patients undergo in-depth testing, like cytogenetics?  

Dr. Betsy O’Donnell:

Yes, so if you’re doing a bone marrow biopsy, absolutely. The question in terms of who needs bone marrow biopsies, if someone has a low risk MGUS, those patients don’t necessarily require a bone marrow biopsy. It’s an invasive procedure, it’s an uncomfortable procedure. But if we’re doing a workup for multiple myeloma or smoldering myeloma that includes a bone marrow biopsy, then absolutely. 

Katherine Banwell:

Okay. Dr. Nadeem, what are you looking for with cytogenetics, and how might test results affect prognosis and treatment? 

Dr. Omar Nadeem:

Yes, so as mentioned earlier, there are some mutations that are considered high risk, I will say with the caveat that we don’t fully understand every single mutation yet or have identified every single mutation yet that may be high risk or low risk.   

But there are roughly five that we have identified that if a patient has one or two or several of those abnormalities, then their disease may behave a little bit more aggressively or may not respond as well to treatment. 

However, I think myeloma is just very complicated, so we look at a lot of these results in the beginning, both whether they may be good or bad. But I think, ultimately, we have to see how patients do, and that by far is the most important prognostic factor, in my opinion. So, if we look at some of these tools, including staging, some of the bone marrow results and cytogenetics, and try to give some prediction in terms of what we may see from this person’s disease, but ultimately the treatments that are so effective now really dictate the course for the majority of the patients. 

Katherine Banwell:

Are there specific tests that patients should ask for that could impact their care decisions? 

Dr. Omar Nadeem:

Yes, I think it depends on where they are in their disease state. So, if we’re looking at whether a patient has a precursor or plasma cell disorder or multiple myeloma, then they need all the testing to help us figure that out. 

So, that includes a bone marrow biopsy, the FISH testing as we just talked about. Advanced imaging like a PET scan or an MRI is now critical to identify patients that may have multiple myeloma versus those that have a precursor condition. So, we used to count on X-rays, as Dr. O’Donnell mentioned, but now really we do prefer one of those advanced imaging techniques for patients to undergo so that we can know. 

So, I think if they have basically those tests completed, that gives us most of the information that we need. 

Katherine Banwell:

Okay. Thank you for that. Let’s go back to asymptomatic myeloma for a moment. Dr. Ghobrial, how are people with MGUS monitored? 

Dr. Irene Ghobrial:

Yes, so how do we even diagnose them, right? It’s a big question because it’s incidentally found. Someone will go to their primary care doctor and have a little bit of a high protein or slight anemia, and it may not be related, and then their doctor will check for serum protein electrophoresis, and that’s pure luck. We want to take away luck from this equation. We want to take away chance from this equation. 

And we want to start screening people who are at risk, and we are doing that with the PROMISE study.  

It’s online available to everyone nationwide, international now, where you can sign up on promisestudy.org and try to ask the question that we do for you research level, the serum protein electrophoresis, and a new test called mass spectrometry that is much more sensitive than SPEP to find it. 

Now, once we find MGUS, we want to know what is my own personal risk of progressing to myeloma? Because I could be 30 years old with MGUS, and likely I will progress to myeloma in the next 10 years, 20 years, and by the time I’m age 60, I would have been diagnosed with myeloma. Just a true case in many, many people. If people are diagnosed today with myeloma, they are going to their doctor because they had back pain or anemia, and they are diagnosed with myeloma. In almost all of the cases, they would have had MGUS and smoldering, but they didn’t know about it three years ago, four years ago because they never got tested  
for it. 

Katherine Banwell:

Right.  

Dr. Irene Ghobrial:

So, we want to change that completely and become proactive rather than being reactive and waiting for symptoms to happen. Once you have MGUS or smoldering, because we don’t know, we start looking for all of the things to help us identify your risk of progression. So, we look at the height of your M-spike. Is it small or big? And then we in many cases say okay, maybe you need a bone marrow biopsy if your M-spike is a little bit on the higher side because we don’t want to miss smoldering myeloma, which will change the prognosis. 

And then we start looking at do you have anemia? Do you have kidney failure? Do you have any of the other things that may predict that you may be actually doing into myeloma? 

We also look at it more as a movie rather than as a snapshot, rather than a picture. If your M-spike is changing or your light chain is changing every three months, every six months, that’s an indicator that the cancer cells are doing something. They’re working in there and growing, and that’s why they’re increasing the M-spike and the light chain. 

And that evolving number is actually a very big predictor of telling us that there is a risk of progressing. Those are all clinical markers that we can do. When we look at the FISH, which we talked about, we can tell the certain markers are chromosomal changes that tell you that those cancer cells want to grow a little bit faster. So, 1q abnormality, 4;14, 14;16, 17p, all of those have been shown that when you have them, the cancer cells are not just sitting around and doing nothing. They’re actually starting to grow, and we want to catch them and understand what is the biology of the disease rather than just how many cancer cells you have. 

We do a lot of research level, and potentially now we’re going to give them back to the patients as clinical level, where we can give you more information about that prediction of your risk of progression. One of my colleagues calls it predicting the hurricane. We know that the hurricane will happen, and it’s a question of how precise could you be? We’re the Weather Channel men here.  

And we could be very precise and tell you it’s going to hit Miami at 2:00 in the afternoon tomorrow, and you could be prepared for it and get out of there. Or, you could be completely unprepared because we were not very accurate in our prediction and tell you it may hit the whole East Coast in the next two weeks. That’s not accuracy. So, we want to be more accurate in our prediction of myeloma because one person will never develop myeloma and can go have fun and enjoy life and not be worried and anxious about their risk, and another person we might say let’s watch you more carefully, or let’s think of interception preventing things. 

So, we do things called next-generation sequencing, taking all of those small numbers of cancer cells, even as little as single cells, and we can do whole genome sequencing and give back that information.  

We look at the immune cells and give back that information. We can do mass spectrometry. And with Betsy and Omar, we’re doing more and more tests so that when we have this prediction model, circulating tumor cells and so on, we can be more accurate in giving you that prediction. 

And help you make the next decision of are we watching carefully, are we preventing and intervening with behavior modification with other things? Are we intervening with therapy to intercept the disease? 

Katherine Banwell:

When are more in-depth tests necessary?  

Dr. Irene Ghobrial:

It depends, of course, on everything. I would probably say for every patient, it is a unique discussion. Some patients will tell me, “Let’s watch again in three to six months, and then I will do more testing,” and some patients want to know everything immediately. And we have those discussions with every patient, and we tailor our therapy as well as our diagnostics workup with every patient, depending on how much they want to know, how much their risk is, and how much they want to be involved in that discussion of how much to prevent myeloma. 

Katherine Banwell:

All right. Dr. Nadeem, as we begin our treatment discussion, would you define personalized medicine as it relates to myeloma care? 

Dr. Omar Nadeem:

Yes. I think we’re getting better and better at really having a personalized treatment plan for each individual patient with multiple myeloma. I think Dr. O’Donnell defined before, we are identifying some of the markers where we have targeted therapy for, and we hope with time we’ll discover more and more targets that can truly lead to personalized medicine for individual patients. 

Right now, though, we have a lot of approved therapies for multiple myeloma, and that list is getting longer and longer basically every month, it seems, nowadays. So, when we have so many tools in our toolkit, we then have to figure out, well, which strategy works for which patient? And the fact that we have effective therapies, we’re able to tailor how much of one particular therapy a patient may benefit from. So, some of the decisions that come into play is which medication should I combine for this patient which will lead to obviously disease eradication? 

And then also, how much do I need to intensify that treatment? Do we need to think about doing a stem cell transplant or not? Yes or no? 

There’s lot of pros and cons, right? So, it’s a very personalized decision that we have, looking at the disease factors, but also a lot of personal factors because transplant interrupts life, and then we have to make sure that that fits with that particular patient’s lifestyle. 

And then we talk about maintenance therapy. You know, that’s the therapy that is designed to kind of keep the disease away usually for many, many years for the majority of patients.  

But what does that look like, right? Does that include just pills? Is it going to be shots plus pills? Is it going to be a combination, etcetera? So, we have all the discussions at each phase of myeloma, and we discuss with them about what the pros and cons are and how that may fit into their particular lifestyle. 

Katherine Banwell:

Dr. O’Donnell, what factors do you consider when choosing a treatment approach? 

Dr. Betsy O’Donnell:

So, I think you’ve heard from all of us that we really try to have an individualized approach. When we’re talking about multiple myeloma, one of the main factors that I think about is really kind of the overall wellness of the patient. Historically we had different categories of transplant eligible, transplant ineligible. 

And so that can influence some of the decisions. Really it comes down to what is the person’s performance does? How well are they doing in their day-to-day life? And that really can dictate the intensity of the therapy. We know that age is just a number, it really is, so there are factors beyond that. What other medical problems do people have? What are the specifics of how well their kidneys are working? 

And so the biggest thing that we can work with is the dose. In fact, we’ve had work that shows that using lower doses from the get-go in older patients allows almost identical outcomes, but really gives patients a tailored dose to where they are at that juncture in their life.  

And so remember, myeloma is much more like a marathon, and so you have to set out at a pace that can be sustained. We treat people continuously. There’s an induction phase where we use a multiple drug combination, but beyond that, as Dr. Nadeem just said, they go on to maintenance, and that maintenance is indefinite. And so you have to set out at a pace or at a dose that you can sustain. 

Different medications have different toxicity profiles, so if someone had, let’s say, cardiac or heart issues, we might steer away from some medications that may exacerbate those. So, every decision is individualized. It’s based on who the patient is, where they are in their life, what other medical problems they have, and what we think they will do best with over time, not just in a short timeframe. 

Katherine Banwell:

Well, as we’ve been discussing, treatment choices vary for individual patients. Dr. Nadeem, what types of myeloma treatment classes are currently available?  

Dr. Omar Nadeem:

Yes. So, we started over three decades ago plus with just having basically steroid medications and some older chemotherapy drugs that weren’t very targeted at all, and that was basically all we had up until about a little over 20 years ago, where immunomodulatory drugs were first discovered to be effective in multiple myeloma, and that included thalidomide and now a commonly used agent called lenalidomide, or Revlimid.  

After that, we had a next class of medications approved called proteasome inhibitors that work differently than the immunomodulatory drugs, and then we combined all of these therapies about a decade plus ago and showed that that was better than anything else that we were doing before that. So, combining the steroids with the immunomodulatory drugs and proteasome inhibitors became the standard of care. 

And then we had the next class of drugs approved in 2015 called monoclonal antibodies, and that’s the first time we have monoclonal antibodies approved for myeloma, and it first started in patients that had relapse myeloma, and then they made it all the way up to front line therapy with a drug in particular called daratumumab.  

And now what we’re going is entering an era of combining all four of these therapies, just like we did 10 years ago with three drugs, and showing that combining four drugs is actually better than three. And the important thing there is that it’s not necessarily adding cumulative toxicity. These are targeted therapies; they all work differently but they all work really well together. So, now combining these agents has allowed us to really treat the disease effectively and allow for patients to tolerate the therapies.  

And then over the last couple of years, we’ve now entered kind of the next renaissance in myeloma where you have immunotherapies, and these are sort of true immunotherapies, in some cases taking the patient’s own T cells and then genetically modifying them to recognize myeloma cells and putting them back into patients. This is called CAR T-cell therapy, and that’s now approved for patients with multiple myeloma.  

And that again, just like the previous drug, sits in patients that have – you know, at a space where patients have had multiple relapses. But we’re now studying that earlier and earlier, and that along with another class of drugs called bispecific antibodies that also use your T cells via a different mechanism. A lot of exciting things going on, and we keep adding to the available agents for this disease.  

Katherine Banwell:

As you say, so many exciting advances. Where do clinical trials fit into a patient’s treatment plan? 

Dr. Omar Nadeem:

Yes. So, clinical trials as a term, a lot of times patients have a lot of questions about what that means. There’s a lot of misconceptions, I would say.  

Sometimes patients think they will get either a placebo and they won’t get the adequate treatment, or that they may not get the right treatment, right, because they’re taking a chance going on a clinical trial. It’s actually the opposite. So, all the trials are really designed to improve upon what we already know works in a particular disease, right? So, when we think about trials let’s say in relapsed myeloma, where the patient has already had some of the approved therapies, we’re looking at the most promising new therapies that have shown efficacy either in the lab or first in human studies and then moving them through the different phases and studying them in more and more patients. 

And that’s how all these drugs get started, right? So, they all get started at that point and then make their way to earlier lines of therapy. 

Then you’re trying to answer different questions as part of clinical trials. So, which one of these therapies can I combine, for example. Which ones can I omit, which ones – so, they’re all sort of getting the standard therapy and getting something either added on top of it or removed, depending on what the question that we’re asking. 

And then in the world that we currently live in with precursor plasma cell disorders, as Dr. Ghobrial mentioned, we have lots of patients that are at high risk of developing multiple myeloma in their lifetime, and that could be in a few years to a decade. And a lot of these therapies are so effective, and we’re now trying to really study some of these rationally in that patient population, so that’s a very different clinical trial, for example, than what I described earlier.  

So, it really depends on what you’re trying to achieve and where you are in the phase of your disease. 

Katherine Banwell:

This next question is open to all of you. Are there therapies in development that are showing promise for patients with myeloma? Dr. O’Donnell, let’s start with you. 

Dr. Betsy O’Donnell:

Yes. So, I think we are so fortunate in multiple myeloma to have so much interest in our disease and so many great drugs developed. So, as Dr. Nadeem was discussing, CAR-T cells are an immunotherapy, the ones that are approved now, we actually are fortunate to have two CAR-T cells approved, target something very specific called B-cell maturation antigen.  

We’re now seeing the next generation where we’re looking at other targets on the same cancer cell, that plasma cell, so those are evolving. 

Same thing is true in the bispecific antibody space. Again, those target BCMA now, but we have newer bispecifics who look at alternate targets, and really what this does is it gives us different ways of approaching the cancer cell, particularly as you relapse through disease. 

Katherine Banwell:

Anybody else? Dr. Ghobrial, Dr. Nadeem? Anything to add about therapies available? 

Dr. Irene Ghobrial:

I would probably say we’re also getting into targeted therapies and more of personalized, so if you have an 11;14 translocation, venetoclax would be an amazing drug for that. And the more we can say my own personal myeloma, what’s the best treatment for me, that’s how we’re trying to do it. So, it may not be exactly precision medicine, but we’re getting closer and closer to precision medicine of my myeloma, my specific drugs. And even if people have a 17p deletion, then we would say let’s think of that immunotherapy.  

It is truly a renaissance for us, and we’re starting to get into trispecifics, into off-the-shelf CAR-T, into so many new things. Into two different antigens that are expressed for the CAR-Ts. I mean, we are really beginning the era of immunotherapy, and we’re excited to see how much we can go into that because it will completely change myeloma, and hopefully we will cure many patients. We think we have already amazing drugs. It’s a matter of when to use them and who is the right person for this right drug. 

Katherine Banwell:

Exactly, yes. Dr. Nadeem, many patients are on maintenance therapy following active treatment. So, how is a patient on maintenance therapy monitored? 

Dr. Omar Nadeem:

Yes, so, majority of the time just with bloodwork. We don’t necessarily need to do a lot of bone marrow biopsies and PET scans for a majority of patients that are on maintenance therapy unless we’re either worried about their blood markers or some symptoms. Generally speaking, any time – it depends on what maintenance therapy they’re on, of course. If they’re just on lenalidomide, which is the most commonly used maintenance therapy, a lot of times we check in with them every one to three months. 

Depending on how their disease status is and how they’ve been doing and whether there’s any side effects that we need to worry about. So, they still have to see their doctors, still have to get the bloodwork. Usually you can get away with having it done no more than once a month or so, unless they are on other medications along with Revlimid, where we then have to check in with them a little bit more frequently. 

And some of that changes, so patients can be on maintenance therapy for five plus years, and we get a very good sense of how they are doing and kind of how their disease is doing, and we can kind of be a moving target in terms of the frequency of the follow-ups. 

Katherine Banwell:

We know that relapse can happen. Dr. Ghobrial, how common is relapsed or refractory disease? 

Dr. Irene Ghobrial:

Yes, and fortunately, we do have amazing remissions. We have very long remissions. Many people are living 10 years, 15 years and longer, which as Dr. Nadeem said, was not something we knew about years ago. I trained 20 years ago as a fellow, and myeloma was a survival of three to five years.  

We’ve come a long way, but we want to change that even better. We want a cure. We want to tell a patient, “You are done. You’re cured,” and we will not stop until that happens. So, when people have a progression again or relapse, then we want to consider what is the next available option. What is the best option to give them yet one more long, long remission? We are failing sometimes, and that’s because the disease is so bad, the biology of the disease is so bad, and the drugs that we’re using may not be the best drugs for that patient. 

And that’s why we need to understand better the biology and pick the right drugs for the right patient up front as much as we can, and also think about earlier treatment. We were just saying we probably have amazing drugs, but we’re waiting way too long until people have almost metastatic disease, and then we treat them. Why not think of an earlier interception when the disease is less mutated, when you have less cancer cells, a better immune system, and use your best drugs then? And hopefully we will achieve cure in many of those patients.  

Katherine Banwell:

What testing takes place after a relapse? Is it different than what has happened before, the testing that was done before? 

Dr. Irene Ghobrial:

No, the same tests exactly. We sort of say it’s restaging. We check everything again – the bone marrow biopsy, the FISH, because you may now develop a 17p that was probably there, but the very, very small number of cells that you cannot detect, and now it grows because of something called chrono selection. The drugs kill the sensitive cells, but they don’t kill the bad cells, and that’s how we can get all of those changes and mutations.  

Katherine Banwell:

Okay. Dr. O’Donnell, is the process for choosing treatment different for a relapsed or refractory patient? 

Dr. Irene Ghobrial:

So, that’s a great question. Yes, it can be. I mean, again, it always depends on how the person is doing at that time. It also depends, there are certain drugs that may not be approved in the front lines, something like venetoclax. If a person has a specific translocation, this 11;14, that’s something that we would like it in a second-line setting, for example. 

Usually one of the big questions people ask is if you’re on a specific class of drugs, should you change classes? So, this example is if you’re on Revlimid, and you have evidence that your disease is progressing, should you change to a different type of drug? A proteasome inhibitor, monoclonal antibody? Should that include one of the same classes of drug, like pomalidomide (Pomalyst), which is the next generation? 

So, there are a lot of different factors that we consider. The number of drugs. So, you know, as Dr. Nadeem said, historically – there’s a lot of history in myeloma therapy, and it’s been an evolution, and so now we’ve had people who were treated with the three-drug combination that are starting, after many years, to progress. So, we might choose a monoclonal antibody for those patients because it wasn’t available at the time they were diagnosed. Versus patients now, who are typically on a four-drug regimen that includes those monoclonal antibodies and all the different classes of drugs. 

We’re looking at different and, if available, novel agents to put those patients on. And again, I think Dr. Nadeem made a really important point that I want to underscore, which is that very often our best therapies are available in clinical trials. And so when and if there is the opportunity to be on a clinical trial, you may be then able to get something that would not otherwise be available to you. So, I encourage people to always have an open mind to being on a clinical trial at any stage in their disease treatment. 

Katherine Banwell:

What therapies are available for relapse or refractory disease? Are they different than other therapies? 

Dr. Betsy O’Donnell:

You know, so that’s a great question. So, yes and no. I highlighted one example that might be a little bit different, but in general, we’re very fortunate that we have multiple classes of drugs, meaning we have different drugs that work differently to kill your myeloma cells. And as Dr. Nadeem said earlier, we use those in combinations to increase the effectiveness of those medicines. Within each class we have a variety of drugs. 

You used the example of immunomodulators, and show that we have three different of those type of drugs. We have two different proteasome inhibitors. Beyond that, we have other classes of drugs that were mentioned. We have monoclonal antibodies, immunotherapies.  

And so very often we make, it’s almost like a mix where we pick what we think is going to be most effective, sometimes based on cytogenetics. The biology. Sometimes based on patient selection. What are their other medical problems, what are their current issues? And we pick the combination that we feel is going to be most effective from the different classes of drugs that we have together, usually trying to use multiple drugs in combination. 

Katherine Banwell:

Well, what newer therapies are available or in development for refractory and relapse disease? 

Dr. Betsy O’Donnell:

So, I think that the greatest interest that I think we’re all most excited about is the immunotherapy space, and I think we’ve seen – for myeloma, we see that this is a relapsing and remitting disease. 

And what’s been so exciting about CAR-T cells and the bispecific antibodies is that in patients who have had, on average, five relapses, we’re seeing tremendous results. So, complete remissions or very good partial remissions that last. In fact, can last up to two years, on average, with one of our CAR T-cell products. 

So, this is really exciting, especially when you compare to what historically has been out there for patients who have had that many relapses. And just as Dr. Nadeem said, the way that drugs enter, they enter from the relapse refractory setting, ethically that’s what makes the most sense, and they march their way forward. And so that process is happening right now as we speak, and I think like Dr. Ghobrial talked about, is the importance in early disease of thinking about using these really exciting therapies in patients who have lower burdens of disease with a goal of cure. 

And so I think all of us on this call are committed to one thing, and that is curing multiple myeloma, and even the precursors that lead up to it so that patients never have to go through the process of years and years of therapy. And so I think we’re very excited about what immunotherapy might be able to offer as we move forward in myeloma treatment. 

Katherine Banwell:

Yes. Thank you for that, Dr. O’Donnell. Let’s take a few questions that we received from audience members prior to the program. Colin writes, “How is it determined as to which patients might be the best candidates for clinical trial CAR T-cell treatment?” Dr. Nadeem, we talked a few moments ago about CAR T-cell treatment. Would you like to answer this question? 

Dr. Omar Nadeem:

Sure, I’d be happy to. So, CAR T-cell therapy is already approved. It’s FDA-approved for patients that have had four or more prior lines of myeloma therapy. So, when we think about a patient coming to us for that particular treatment that have relapsed myeloma, we’re always looking to see how much of the previous therapy they had. 

Whether they meet the indication, the labeled indication for that particular product. And then now, as we’ve discussed today, we’re studying this CAR T-cell therapy in various different phases of myeloma. Earlier lines of therapy, even thinking about studying it in high-risk smoldering myeloma, right? And then kind of looking about how we can best study this therapy in so many different phases.  

So, it all depends on where a patient is in their disease state, and then we kind of look to see whether a commercial approved CAR-T product makes sense for them, or we think about one of our several relapse CAR T-cell trials that are looking at BCMA target, which is what the approved one is, but also looking at newer targets like GPRC5D that we’ve brought up before. 

So, it encompasses a lot of different things, that question, but I think in terms of the candidacy of the patient itself, we do know that these CAR T-cell therapies have some toxicity, so we have to then weigh in terms of what medical problems they have whether they’ll be able to tolerate what the majority of patients with CAR T-cell therapy get, which is this syndrome called cytokine release syndrome, where patients will get a fever. 

And in some cases have changes in their blood pressure or oxygen levels. We have to make sure that the patient’s body can handle that. I will say we’ve gotten better and better at managing a lot of toxicities as it comes to CAR T-cell therapy. When this was first approved, it was all pretty new, but now what we’re learning is if patients are developing a fever, which the majority do, we’re intervening earlier and earlier to prevent them from getting sicker. 

So, these are things we’ve learned now, and the majority of patients get through CAR T-cell therapy toxicity period much better than they did when it was first approved. 

Katherine Banwell:

Okay, thank you for that.   

Dr. O’Donnell, Alex wrote in with this question. “What is the difference between a complete response, VGPR, and PR as it applies to prognosis and maintenance after an autologous stem cell transplant?” And before you answer the question, would you define VGPR and PR for us?  

Dr. Betsy O’Donnell:

Sure. So, we have different criteria that help us understand how well a drug is working, and they’re uniformly used across clinical trials so that we’re all speaking the same language. And so we talk about a PR, a VGPR, and a CR. So, a CR is a complete response, which is 100 percent of that monoclonal protein that we initially detected is gone. We can’t measure it. Or if you have an elevated light chain, which is another piece of the protein, that has gone back down to normal.  

Taking that a step further, astringent CR is if we do a bone marrow biopsy and we can’t find any cancer plasma cells in there. A VGPR is where we see a 90 percent reduction in the amount of protein we can measure, and a PR is anything over – a partial response is anything over 50 percent. 

So, that’s a language we speak really just so that when we’re interpreting clinical trials, we all are using the same criteria. 

And so these are different terms that classify it. If the example that you gave, someone’s had a transplant, what would typically happen 100 days after that transplant is a patient would restart maintenance therapy. The classic maintenance is just lenalidomide, which is the pill that they were probably taking before that. And there’s a lot of controversy now but no good answers about changing therapy after a transplant, if you haven’t received a deep response. 

What we do know is that after a transplant, when someone goes on lenalidomide maintenance, they continue to respond. So, the greatest depth of response is not necessarily achieved in the induction phase or right immediately after transplant, but over time on maintenance. 

There’s another tool that we’re now using and incorporating, both in terms of how we assess treatment but also potentially in how we modify treatment, which is something called minimal residual disease, MRD, which goes a step beyond. When people have astringent CR, a CR, looking for really just traces of the disease on a molecular level.  

And all of those help us understand how well the patient has responded and how long that remission might last, but they’re not definitive in terms of how we should adjust treatment based on those right now. 

Katherine Banwell:

Okay. Thank you for that. Dr. Ghobrial, this is a question we’ve received from Carlene. “Many prominent doctors claim the COVID vaccines suppress the immune system. How can boosters be justified in an already immune deficient myeloma patient? 

Dr. Irene Ghobrial:

Yes, so we think that protecting yourself and preventing COVID infections is so essential and so important. 

Especially in a patient with myeloma and especially when you’re receiving therapy: daratumumab, bispecifics, CAR-T. We want to make sure everyone is protected from COVID infections, and they are real. They are serious, and they cause death in our patients. So, every step, not only getting the vaccine but also sometimes we give tixagevimab co-packaged with cilgavimab (Evusheld) to protect our patients and protect further problems and reinfection. 

Katherine Banwell:

Remind us, what that is, the Evusheld? 

Dr. Irene Ghobrial:

Oh. It’s an antibody to help us prevent the COVID infection, so as a prevention method rather than as a treatment method.  

The other thing that we think of is the immune system is already altered in myeloma. It’s even altered or changed even as early as MGUS and smoldering myeloma. So, when we’re walking around and thinking, “Oh, I have only a benign design of MGUS,” that’s not true. The immune system has already started to change as early as MGUS, and in many of us as we get older. 

So, we have to be more protective and we have to be more careful with our patients. But as we get to even myeloma, before we even treat it, before we use the drugs that kill plasma cells, good and bad plasma cells, which secrete antibodies that fight infections, we are already at risk for COVID infections. 

And then our drugs, unfortunately, don’t only kill the malignant or the bad plasma cells, they also have a small side effect of killing also your normal plasma cells, and these are the ones that make antibodies to fight infections. So, you are at risk and you have to be very protective and careful with yourself. 

Katherine Banwell:

Is there any research on predicting hereditary risk of myeloma? 

Dr. Irene Ghobrial:

Yes, so part of the PROMISE study is trying to understand what is the risk of developing myeloma. So, we’re recruiting people who are either African American because they have a three times higher chance of developing myeloma compared to the White population, as well as people who have a first degree family member with a plasma cell disorder.  

Or even any blood cancer because now we see that CLL and lymphoma and myeloma can actually come together. And we’re now doing something called whole genome sequencing of all of the DNA that you inherit from Mom or Dad called the germ line. Basically, we try to see did you inherit the gene from Mom or Dad that increases your risk to myeloma? 

Now, it’s not as high as something like BRCA1 mutation or 2 mutation, where if you have that, you’re high, high chance of developing breast cancer or ovarian cancer and so on. We probably have several factors that need to be put together. You inherit something and then the environment adds something, and then as we get older, we get the hit. 

Or you inherit something that changes your immune system, and that allows the plasma cells to start proliferating faster because they are reacting as an immune cell, and that allows the hit of myeloma to happen. And we’re working on that, and we would really encourage everyone who has a relative with myeloma, sign up on PROMISE study. 

Because that’s how we can get the answer. That’s how we can say it’s not because you are an African American or you’re White. It’s not because you have a first-degree family member or not. It’s because of this gene. So, taking away race, taking away all of those factors, taking away age and trying to go back to the biology. Is it a certain gene, is it the certain immune cell that makes us go to that risk? 

And then Dr. O’Donnell is really taking it to the next level. Now what is in the macro environment? So, we talked about what we inherit, but it’s like nurture and nature, right? So, nature is the genetics and then nurture, what do we eat? What do we change? Obesity, health, all of those things change our inflammation level and change our ability to basically prevent those myeloma cells from starting or from continuing to progress. And she can potentially talk about her work on microbiome, on the tiny bacteria that are in our body from what we eat. So, maybe, Betsy? 

Katherine Banwell:

Okay.  

Dr. Betsy O’Donnell:

Absolutely. Yes, so one of the things that particularly interests me is the effect of lifestyle on our risk of getting cancer. 

And specifically within plasma cell disorders, and I think there have been other cancers, breast cancer and colon cancer, where they’re a couple steps ahead of us just in understanding the influence of things like obesity and the gut microbiome. So, the specific bacteria that are within your intestinal tract. It makes a lot of sense in colon cancer, but we think that that’s not limited to diseases like that. We actually think that these microbiomes, which are influenced by the foods that you eat, may have a relationship with your immune system. And remember, myeloma is a cancer of the immune system. 

So, we’re all working together on our team here on a very scientific level to understand lifestyle influences and how they may cause or potentiate multiple myeloma. And so we’re excited to kind of bring this piece together. When you think about the spectrum of plasma cell disorders, not everybody goes on to myeloma, but a lot of people sit in these early precursor diseases, MGUS and early smoldering. 

And so are there things that people can do for themselves that might influence their gut microbiome, or if it’s the amount of body fat that we have that’s very involved in cell signaling? Can we modify those things, exercise more potentially, that will decrease our body inflammation levels or alter those pathways that have been set in process that, by altering them, may decrease the risk of going on to more advanced plasma cell disorders? 

Katherine Banwell:

That’s such great information. Thank you for answering that, and thank you all for your thoughtful responses to the questions.  

As we close out the program, I’d like to get a comment from each of you. As I mentioned at the start of the webinar, care for myeloma patients is becoming more personalized, and we’ve been talking about that throughout the program. What are you hopeful about the future of care for myeloma patients? Dr. Ghobrial, do you want to start? 

Dr. Irene Ghobrial:

I’m hopeful that we truly cure myeloma, and no one should ever develop end organ damage. 

We should identify it early and treat it early, and no one should ever come in being diagnosed with multiple myeloma. 

Katherine Banwell:

Okay. Dr. Nadeem? 

Dr. Omar Nadeem:

Yes, I think I definitely agree with what Irene said, and really having a more thoughtful approach to each individual myeloma patient. As I mentioned earlier, we have so many available therapies. I want to be able to know exactly which patients need which path in terms of treatment, and which ones we can maybe de-escalate therapy, right? So, thinking about which patients do well and maybe can get away with not being on continuous therapy, and those that absolutely need it. Identifying them better to give them the best therapy. 

Katherine Banwell:

Dr. O’Donnell, do you have anything to add? 

Dr. Betsy O’Donnell:

I think we all share a common goal, which is cure, and for those who we can’t cure yet, I think really working on making the experience as good as it possibly can be and focusing on the factors that we can control and optimizing those, both for patients and their caregivers who are in this journey together with the patient. 

Katherine Banwell:

Well, I’d like to extend my thanks to all of you for joining us today. 

Dr. Irene Ghobrial:

Thank you. 

Dr. Betsy O’Donnell:

Thank you for having us. 

Katherine Banwell:

And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks so much for joining us.  

 

Thriving With Lung Cancer: What You Should Know About Care and Treatment

Thriving With Lung Cancer: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with lung cancer? Dr. Jyoti Patel discusses care and treatment goals, reviews current and emerging treatment options, and shares advice for living well and thriving with lung cancer.

Jyoti Patel, MD, is Medical Director of Thoracic Oncology and Assistant Director for Clinical Research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. She is also Associate Vice-Chair for Clinical Research and a Professor in the Division of Hematology and Oncology at Northwestern University Feinberg School of Medicine. Dr. Patel is a leader in thoracic oncology, focusing her efforts on the development and evaluation of novel molecular markers and therapeutics in patients battling non-small cell lung cancer. Learn more about Dr. Patel.

See More from Thrive Lung Cancer

Download Resource Guide

Related Resources:

Why Lung Cancer Patient Advocacy Is Essential

Expert Perspective | The Value of Empowering Patients

Collaborating on Lung Cancer Treatment Decisions With Your Team


Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar focuses on how patients can aim to live well and thrive with lung cancer. We’re going to discuss treatment goals and the importance of patients playing an active role in their care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Jyoti Patel. Dr. Patel, welcome. Would you please introduce yourself? 

Dr. Patel:

Hi. Thanks so much. My name is Jyoti Patel. I’m a professor in medicine at the Northwestern University Lurie Cancer Center and I’m the medical director of thoracic oncology and the vice chair of clinical research for the Department of Medicine.   

Katherine:

Well, thank you so much for taking the time out of your busy schedule to be with us today. Since this webinar is part of PEN’s Thrive series, I’d like to ask you from your clinical experience and perspective, what do you think it means to thrive with lung cancer? 

Dr. Patel:

I think our definition of that has evolved considerably over the past two decades. The advancements in the lab and in clinical trials have translated to vastly different outcomes from our patients than I ever imagined two decades ago. So, certainly we see a large number of lung cancer survivors, people who have had early disease that has been eradicated and they are living after their lung cancer diagnosis with sequela treatment. And we see an even larger number of patients who are in active treatment, those with more advanced disease.  

When we can minimize the toxicities of active treatment and really focus on quality of life, survival outcomes, then I think we’re really talking about thriving with lung cancer.  

Katherine:

Mm-hmm. Well, thank you for your insights. Of course, an appropriate treatment course is part of thriving. Before we get into treatment though I’d like you to walk us through the types of lung cancer if you would.  

Dr. Patel:

Sure. So, over 200,000 Americans will be diagnosed with lung cancer this year. And we break lung cancer down into two major diagnoses. So, the more common one is non-small cell lung cancer. The less common one, which accounts for 13 percent of diagnoses, is small cell lung cancer. Those are descriptive terms but don’t really go beyond that. It’s, essentially, what do the cells look like under the microscope? We know that these two behave very differently. Small cell lung cancer tends to be a cancer which can move a little bit more quickly. It tends to be more aggressive.  

We have certain treatment regimens that are appropriate. Non-small cell lung cancer is one which we further subdivide into adenocarcinoma, squamous cell cancer, or large neuroendocrine cancer. And we treat those a little bit more similarly with different local therapies and different systemic agents.  

Katherine:

Okay. How would you define treatment goals for people with lung cancer? 

Dr. Patel:

So, we hope that the number of patients that we find with earlier stage disease increases as we now at least have evidence to do screening for people who are at high risk. So, for patients with early-stage disease, which we really define as stage I and stage II – so, cancer that’s limited to the lobe of a lung – our best treatment options are surgery and sometimes radiation in appropriate patients. And for those patients, we think that treatment is discreet and curative.  

For the third of patients who present with stage III disease or locally-advanced disease – and here we’ve seen significant advancements with the integration of immunotherapies, improvements in surgery, and radiation. Their treatment course tends to be a bit longer but, again, our intent is curative. So, the cancer has discreet therapy, we complete it, and then patients are in survivorship mode, in which we’re following them periodically.  

Unfortunately, still, a large number of patients present with more advanced disease. Stage IV disease or metastatic disease. Those are all sort of interchangeable. And treatment for those patients is about controlling the cancer. Often, you’ll hear the word “palliative.” So, the goal of treatment is to control the cancer, to decrease the burden of cancer, and to help patients live longer. Certainly, again, with our advancements of immunotherapies and targeted therapies, patients are living longer than ever before.  

And in some patients, it really becomes a chronic disease in which checkups can be periodically done or patients can be monitored off of treatment for long periods.  

Katherine:

Mm-hmm. Do treatment goals vary by lung cancer type?   

Dr. Patel:

So, the goal of cancer treatment is always to make patients live longer and to make sure that that quality of that survival is the best it can be. So, that’s always our overlying goal. For patients with early disease or early stage – stage I to III non-small cell lung cancer – is something we call limited stage. Small cell lung cancer, the intent is, again, curative. For patients with more advanced disease, we tend to think about the cancer as something that we control, that we see a good response to hopefully, and watch patients over time.  

There are a subset of patients with more advanced disease that have really significantly better outcomes. We call these sort of patients “super survivors.” And we hope to make that number greater as we incorporate new science into their treatment paradigms. 

Katherine:

What is the role of patients in making treatment decisions? 

Dr. Patel:

I think all treatment decisions are patient-focused.  

So, again, understanding someone’s goals of treatment are important. But understanding the context in which the cancer is happening. So, the cancer is part of a patient that has a really full life. Family. Work. Other medical comorbidities. Things that they prioritize. And so, having open discussion about the likelihood of achieving curative therapy or what the risks and benefit ratios are in palliative therapy are absolutely essential to having transparent and honest communication with patients. But it is also optimistic and compassionate.  

Katherine:

You mentioned some treatment approaches a few moments ago, but I’d like to walk through the types of treatments that are used today to treat lung cancer. Let’s start with surgery.  

Dr. Patel:

We think about local therapies as things like surgery. So, surgery has evolved, again, significantly.  

Now with videoscopic approaches and robotic approaches we’re able to remove a tumor either with a larger incision – more traditional incision – or some of the smaller incisions. And the goal of doing the surgery is often to want to diagnosis the cancer. So, to do a biopsy. But when it’s used in terms of cancer treatment, the goal of surgery is to get a complete resection.  

So, we only do surgery if we can remove a tumor and mass with clear margins and not compromise other vital functions. Sometimes we’ll, again, do a more palliative surgery if we need to, if there’s a problem that’s causing significant symptoms. But in that case, the surgery is generally not improving the survival of the patient. It’s trying to palliate symptoms.  

Katherine:

Mm-hmm. What about other types of therapy? 

Dr. Patel:

Other localized therapies predominately include radiation therapy. And, again, radiation has significantly changed over the past years. We’ve been able to incorporate new technologies, truly target tumors, and to minimize toxicity, with two kinds of radiation. Photon therapy, which is more traditional therapy, and proton therapy, which we see administered in a very small subset of patients.  

Primarily, photon therapy, we treat tumors, sometimes over many weeks, to decrease toxicity versus sometimes we give one or two doses of radiation in a high-dose fashion that’s very targeted.  So, often for the chest in stage III cancer, for example, a patient may end up getting six weeks of radiation Monday to Friday with chemotherapy.  

And that, again, is curative intent. It’s to ablate the cancer and to provide the best local treatment. 

Often, we’ll do something called stereotactic radiation therapy. And that is if there is a discreet mass, often that could be if the cancer is metastasized to the brain, we can give very targeted radiation there, again, to ablate the tumor.  

In patients who may not be candidates for surgery because lung surgery is a big deal, right? Removing part of your lung can lead to morbidity in someone with other medical issues. Sometimes we can use pinpoint radiation in the lung and see really good outcomes for patients with good disease control.  

Katherine:

You’re also using chemotherapy still, I would imagine? 

Dr. Patel:

The other part of treatment for lung cancer are systemic therapies. And there a number of systemic therapies. So, I sort of break it down into three major parts. One is chemotherapy. Chemotherapy remains a backbone of treatment for lung cancer.  

It’s a lot more tolerable and much more personalized than ever before. Often chemotherapy can be given to patients without significant toxicities. Not everyone loses their hair. Not everyone has neuropathy. Often, I have patients who are working and taking care of their families on chemotherapy. So, it is a good and very reasonable option. But two things that we’re really most excited about – and I think have changed the field most dramatically – are targeted therapies and immunotherapies.   

Katherine:

Mm-hmm.  

Dr. Patel:

These targeted therapies are rationally-designed molecules or antibodies that block proteins that may be overexpressed in lung cancer.  

So, some of them are the byproducts of mutated genes that are upregulated and causing a cancer to grow. Others may just be that we’re seeing a high level of protein expression on the cancer cell. But these targeted therapies preferentially bind to their targets that are present on cancer cells and not so much normal cells. Because of this, often there is less toxicity to normal cells. But because we can find specific targets – and the best targets are ones that are only expressed on cancer cells.  

But because we can find a direct target, sometimes we’re able to design drugs that may have significant efficacy. So, 80 percent or 90 percent of people who have a particular target and are able to get a targeted therapy may have a response to treatment. Targeted therapy can be great for some patients. And patients may be on oral medications, sometimes for years, to control their cancer.  

The other real game-changer in the past decade for lung cancer has been the integration of immunotherapy. Approved immunotherapies currently are primarily antibodies that we give to patients. And these antibodies block proteins that are expressed by cancer cells which downregulate the immune system. By shutting down these proteins, your own immune system is able to kind of re-see the cancer cell and kill it.  

And so, now we know in patients with more advanced disease that immunotherapy or immunotherapy with chemotherapy leads to better outcomes than we’ve ever seen. We also use immunotherapy for patients with stage III lung cancer after chemotherapy and radiation. And this improves their survival significantly.  

And most recently, we’ve now integrated immunotherapy after surgery for patients with early-staged disease to decrease their chance of relapse from cancer.   

Katherine:

Mm-hmm. That’s excellent. Are some of the targeted therapies taken orally? And if so, are patients in charge of administering them, their own therapies?  

Dr. Patel:

Many of the targeted therapies that are most effective are taken orally. And so, patients take them at home. Often, they’ll have once-daily dosing or twice-daily dosing. The number of pills often depends on the formulation of the drug. So, patients are responsible, I guess, for taking them. That comes with a lot. So, we need to think about, how do we help with adherence? How do we manage toxicity? How are the drugs affected by whether you eat or take the drug on an empty stomach? There are a lot of nuances there.  

Generally, we like to give a lot of information to our patients. So, often, patients will meet with a pharmacist when they’re first prescribed the medication. They’ll meet with our nurses to go over how to take those and how to manage any side effects if they have them or what to do if there are any adverse reactions.  

Katherine:

Mm-hmm. Well, what would happen if a patient forgets to take one of their medications? Does that impact its effectiveness? And then should they get in touch with their healthcare team to let them know? 

Dr. Patel:

So, generally, we like patients to take the medication almost at the same time every day. We sort of think about half-life. So, we want to make sure that that serum level stays appropriate. If someone misses a dose – which happens – and, again the best-case scenario is that people are on these pills for years, right? For several years. So, of course, you’re going to miss a dose.  If that happens, we generally tell people never to double up.  

To let your team know. Often you can just skip that dose and take it in the evening or the next day.  

Katherine:

I’d like to talk about emerging treatments. Are there any therapies in development that patients should know about that you’re excited about? 

Dr. Patel:

There are a number of things that are happening right now in the landscape that is really, again, giving us great optimism about how to move forward. So, areas of active research really concentrate on identification of new targets so that we have identified oncogenes that we’re trying to treat effectively. So, those are things like EGFR Exon 20 mutations or HER2 mutations, as well as some of these new fusions.  

Another area of rapidly growing research is that most patients who have targeted therapies will eventually develop resistance. And so, understanding how to mitigate resistance or how to overcome resistance is important. And we often talk about the different drugs in development as first, second, and third-generation drugs in the EGFR space, which accounts for about 15 percent of lung cancers in the United States. We’re looking at fourth-generation tyrosine kinase inhibitors. They’re certainly very exciting.  

The other piece, I think, of research that is moving and that we are looking forward to understanding why some patients have really robust responses to immunotherapies and others don’t. Or how people become immune to the effects of immunotherapy. And so, understanding the tumor microenvironment, seeing if there are other proteins that we can co-stimulate to cause these robust and durable responses to immunotherapy is an area that we’re working on.  

Katherine:

Mm-hmm. Since no two people with lung cancer are the same, how do you decide which treatment is best for each patient? 

Dr. Patel:

So, the process of evaluating a patient can actually take a little bit of time. So, we first meet a patient, and they may have suspicious findings. We want to understand the full stage of their cancer. And so, in 2022, that’s doing an MRI of the brain, a CT of the chest and abdomen, and often times a pet scan to look for any evidence of distant disease.  

So, once we have radiographic modeling of where we think the tumor is, sometimes we need to do a repeat biopsy to confirm whether or not lymph nodes are involved or the cancer has spread. After we do the biopsy and say that it’s non-small cell lung cancer or small cell lung cancer, we make decisions about looking for genetic markers.  

And so, we’ll often take the tumor tissue and stain for things like PD-L1, which is a marker of response to immunotherapies.  

Very importantly, with all these new targeted therapies, we want to understand the genetic makeup of cancer. So, we want to look for things like EGFR mutations or ALK translocations which are more effectively treated with targeted therapies than chemotherapy or immunotherapy.  

So, those are the two tumor characteristics. But, again, I’ve said before, a tumor exists in a person.  

And so, you need to understand what’s important to the person, what do they prioritize, what’s their health like, what, again, are the preferences, are there other comorbidities that could perhaps make some treatments more difficult? Many people, for example, have autoimmune disease. And so, that can be something that’s relatively minor, like some psoriasis that is well-controlled versus perhaps lupus which can cause organ failure.  

Often with psoriasis there are ways that we can give immunotherapy safely. Sometimes other autoimmune diseases would put patients at very high risk with immunotherapies. And so, again, understanding the overall health, understanding other competing causes of toxicity, are absolutely important as you make decisions together.  

Katherine:

Yeah. It seems like we’re getting closer to personalized medicine. For you, how would you define that term? 

Dr. Patel:

Personalized medicine comes in two forms. So, one is the biologics of the tumor itself. So, what do I understand about the genetic markers, the likelihood of response to the available therapies. The other piece, again, is personalizing it to the person that has the cancer.  

And so, again, what are the preferences? What are the risks they’re willing to take? What are their goals? What are the preferences? 

Katherine:

Symptoms and side effects can sometimes be a burden to patients undergoing treatment. What are the most common issues that patients face? 

Dr. Patel:

So, common symptoms from treatment can include fatigue, lack of appetite, disinterest in the things that made you really excited before. Infrequently now we have severe nausea, because we have such good antinausea medications.  

Sometimes we’ll have problems with blood counts or risks of infection. All of these vary by the treatment that’s rendered. And so, often it may be that you’re on a targeted therapy. Some targeted therapies, for example, can cause swelling in your legs. Immunotherapies are generally well-tolerated but can cause significant side effects in a small minority of people that could include inflammation in the gut, for example.  

So, everything is sort of tailored, I would say. Most frequently, I hear about the fatigue, and then the ongoing stressors of living with cancer. So, the financial toxicity certainly. These drugs are expensive. But not only that, often people have changed the way they work. Their family members have changed how they work to support their loved one. So, bringing people to appointments.  

There’s a lot on someone’s plate. And that can contribute to fatigue and even some anxiety.  

Katherine:

Yeah. What strategies are in place to manage symptoms and side effects? 

Dr. Patel:

So, having a patient who’s knowledgeable about potential side effects and a good advocate for themselves is probably the best way to manage therapy. So, ongoing dialogue with your clinical team, with your nurse, with your physician, are absolutely important. But most of us work with teams of healthcare workers. And so, when I think about our clinic, we have financial counselors, we have social workers, we have dieticians and nutritionists, we work with physical therapists. And importantly, we work with a palliative care team that helps us, again, manage some of the toxicities of therapy.  

We think that they provide a longitudinal assessment of patients and remember what’s most important to a patient over time. Whereas often in the moment there’s this, we want to make the tumor shrink. We think about what we can do immediately. It’s often really helpful to have another team that can provide support over the patient’s journey to help us, again, prioritize what they wanted to do the most.  

Katherine:

Mm-hmm. Dr. Patel, why do you think it’s necessary for patients to tell their doctor about any issues they may be having? Even the little ones.  

Dr. Patel:

I think most of us want to be good patients. And so, we minimize things because we think that, okay, we’re using precious time to talk about things that may seem minor. But, again, all of these add up.  

Even minor symptoms, particularly in the era of immunotherapy, can turn out to be big problems. So, as I say now to my patients particularly on immunotherapy, if something seems a little bit off and you can’t put your finger on it, I just need to know so I can at least do the appropriate workup to make sure that we’re not missing anything. Because symptoms of underlying problems can be very misleading.  

Moreover, I think the cumulative burden of cancer. So, again, we talked a little bit about the financial toxicity, the emotional cost, the time involved in treatment, all of that adds up. And you never want to get it to a breaking point. We want to manage it early on, so we can, again, make decisions together and keep wellness and the quality of survival at the forefront.  

Katherine:

Mm-hmm. You mentioned that sometimes treatment doesn’t work for an individual patient. So, are there options for relapsed patients? 

Dr. Patel:

So, absolutely. Most of our therapies in the metastatic setting work for some time. And then cancer is a difficult adversary. It figures out how to overcome whatever strategy we’re using and becomes resistant. When that happens, often we need to change course. We need to try a new therapy. We have a number of therapies that we’re looking at in the first- and second-line settings. And we’re trying to understand best therapies for subsequent lines of treatment.  

Generally, I say treatment is appropriate if you’re feeling pretty well, right? If you’re able to tolerate treatment, then the likelihood that you would be able to benefit from therapy is significant. How that changes over time weighs heavily on our decision. So, if someone’s having more fatigue or more symptoms from their cancer, it may be that even a little bit of toxicity proves too much.  

Whereas if someone is feeling still really good, we may be willing to say, okay, I’m going to take a little bit more of a risk for the benefit of improved cancer control.  

Katherine:

Mm-hmm. You talked about this a few moments ago, but I would like to talk about self-advocacy. Managing the worry associated with a diagnosis or concerns about progression can lead to anxiety and fear in some patients. So, why is it important for patients to share how they’re feeling with their healthcare team? And who all is in the healthcare team who would be able to help a patient? 

Dr. Patel:

So, the anxiety of cancer therapies, of CT scans, of tumor assessments, can be overpowering. And then the longer-term anxieties. Who’s going to care for me, who’s going to care for my family, am I doing the things that are important to me, are ones that weigh heavily on all of us.  

So, certainly, again, carrying these anxieties over a long time have adverse impacts. So, people who are more anxious may not sleep as well. They may lose weight. They may not be as robust. And so, all of those things weigh into our ability to give more treatment. So, we want people to be psychologically well. We have, generally now in our healthcare teams, a number of people who are there to help.  

And so, we have nurse navigators. Most cancer centers have a number of psychologists and psychiatrists that work with our teams. But more than that, even things like nutritionists and social workers make a significant impact. And then I’m surely lucky to work with a world-class palliative care team. So, these are doctors that really focus on symptoms of cancer, the toxicities of treatment. And we work together to ensure the best outcome for our patients.  

Katherine:

Dr. Patel, we’d be remiss if we didn’t bring up financial concerns.  

Treatment and regular appointments can become quite expensive. So, understanding that everyone’s situation is different, where can patients turn to if they need resources for financial support?  

Dr. Patel:

When your team first talks to you about therapies, it’s important that they have transparency about what something may cost or the risks that you may incur by starting treatment. However, most of us have access to wonderful financial teams and financial counselors that can help you manage this.  

Many of our industry partners and friends are able to have assistance programs to provide oral drugs at discounted rates or to work, again, with organizations in which you may be able to have reduced rates for many of your drugs. Most of the infusional drugs, again, should be covered by insurance. But outside of drug costs, there are a lot of other costs.  

So, parking every time you come for a doctor’s appointment. Time off from work. Time that you’re hiring a babysitter to take care of your children when you’re at treatment. All of those add up. And so, again, perhaps talking to the social worker at your cancer center or talking to the financial counselor, there are often local programs that can help ease some of those burdens. 

Katherine:

Thank you for that advice, Dr. Patel. Before we close, I’d like to ask, are you hopeful about the potential for people with lung cancer to thrive? 

Dr. Patel:

Absolutely. The future is bright after years of working and really developing this great foundational science.  

We are seeing the transformation of cancer care in a way that is faster than I could’ve ever imagined at the beginning of my career. We’re bringing scientific insights to the bedside. And bringing it to the bedside is impacting how patients live with their cancer and thrive with their cancer. They’re living longer and with fewer toxicities and side effects than I ever imagined.  

I’m optimistic about the promise of early detection through blood tests one day, through screening with CT scans to find early-staged disease in which the cancer is the most curable. And then for patients with more extensive disease, to really understand how we can sequence therapies or deescalate therapies when patients have minimal burden of disease, again, to decrease the toxicities.  

Katherine:

Mm-hmm. Dr. Patel, thank you, again, for being able to join us today. It’s been a pleasure.   

Dr. Patel:

Thank you so much for this invitation. I really enjoyed speaking with you.  

Katherine:

And thank you to all of our partners. To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.  

Thriving With Lung Cancer: What You Should Know About Care and Treatment Resource Guide

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What Tests Are Essential Before Choosing a Myeloma Treatment Approach?

What Tests Are Essential Before Choosing a Myeloma Treatment Approach? from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan, a myeloma specialist, discusses the types of tests that myeloma patients should undergo before choosing therapy, at diagnosis, and if they relapse.

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

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How Do Test Results Impact Myeloma Treatment Options?


Transcript:

Katherine:

What testing should take place before choosing a myeloma treatment?  

Dr. Khan:

I thought I could answer this question in an indirect way first.  

Katherine:

Okay.  

Dr. Khan:

I just wanted to let the audience know that anyone, including those that are not in the medical field, can create an account with the nccn.org. That’s the National Comprehensive Cancer Network’s website.  

And from there they can download the myeloma guidelines, which are available to all myeloma providers as well. And in the guidelines, there are sections for workup, treatment, how to follow patients with myeloma, and many other things.   

So, going back to the question, the first patient encounter will likely include a thorough history and physical exam. Initial lab work includes blood counts, the serum chemistries so we know about the liver and kidney function, multiple myeloma markers. And patients about get very familiar with monoclonal protein, the serum immunoglobulins, and the serum-free light chains. 

These are used as the surrogates for responses when you’re undergoing treatment for the myeloma. We will also at the first visit probably also do a 24-hour urine collection, and that’s looking for the abnormal protein in the urine.  

There’s imaging. In the past, we used to do x-rays head to toe. That’s sometimes called the myeloma survey or the skeletal survey. But the new recommendations are actually looking for something a bit more sensitive.  

So, at our practice, what we do is a PET scan.  

So, that includes functional information as well the images themselves. And some institutions may do a PET scan head to toe using low-dose radiation. The final test we will do in patients with newly diagnosed myeloma is a bone marrow biopsy and an aspirate. 

So, the biopsy’s looking at the bone itself and the architecture. And the aspirate, you take the liquid part of the bone marrow, and you can ascertain a lot of information including the burden of myeloma when the patient’s newly diagnosed.  

Katherine:

What do you mean by “burden”?   

Dr. Khan:

You can quantify the number of cancerous plasma cells in the bone marrow. So, some of the information says you have a healthy amount of good bone marrow cells, 50 percent, 60 percent, for example, but of that 50 percent, 60 percent, maybe 80 percent is taken over by myeloma. So, you will get burden of myeloma information from there.  

Katherine:

What additional testing should take place following a relapse?  

Dr. Khan:

I’ll start that response by first talking about the types of relapses, and there are two broad categories. If we see the myeloma coming back as just the monoclonal protein going back up from its lowest, or maybe the serum-free light chain going up – and there are very specific criteria for what defiance a relapse. But if it’s just a number, we call it a biochemical relapse.  

On the other side, there’s a clinical relapse. And at that point, there might be new end organ damage. We’ve heard of the acronym CRAB when we’re describing myeloma. That stands for hypercalcemia, renal or kidney insufficiency, anemia, and bone disease. So, these are end organ damage directly from the multiple myeloma. 

So, typically, we’ll try to change the management at biochemical relapse, because a new organ injury may contribute to the patient’s frailty, or it might even limit the treatment options. The testing out of relapse is pretty similar to the first diagnosis. We’ll repeat the history and the physical example, the labs, imaging. And more often than not, I’ll also recommend a bone marrow biopsy to see is that myeloma changing genetically, and does it help me kind of determine new treatment options.  

How Is Relapsed/Refractory DLBCL Treated?

How Is Relapsed/Refractory DLBCL Treated? from Patient Empowerment Network on Vimeo.

What options are available if a diffuse large B-cell lymphoma (DLBCL) patient doesn’t respond to treatment or relapses? Dr. Justin Kline discusses potential next steps in treatment for DLBCL patients with relapsed or refractory disease. 

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

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Transcript:

Katherine:      

Let’s talk about if someone doesn’t respond to initial treatment or they relapse. Let’s start by defining some terms for the audience. What does it mean to be refractory?

Dr. Kline:       

So, refractory is a term that’s used to describe a situation where a person has received treatment but that treatment hasn’t worked as well as we have expected. And the most – probably the most important scenario is after initial treatment.

Most people, for example, who receive R-CHOP, somewhere between 80 and 85 percent will have a completely negative PET scan after treatment. That’s remission. If the PET scan is not negative and you do a biopsy and it shows that there’s still lymphoma there, that’s what’s called primary refractory. In other words, the person’s lymphoma was refractory to initial or primary treatment. And in clinical trials that are testing agents, drugs or immunotherapies in folks who’ve had multiple treatments, usually refractory is used to define someone who has either not responded or has had a very, very short response to whatever the last treatment they had was.

Katherine:                  

How does relapse then differ from refractory?

Dr. Kline:       

So, right, so relapse suggests that the lymphoma at some point was in a remission, right?

And so for example, a person gets six treatments of R-CHOP, has a PET scan at the end, the PET scan is clean. We say you’re in remission. Eight months later, the person develops a newly enlarged lymph node, and a biopsy shows that the lymphoma has come back, right? That’s what we would call a relapse. There was a period of remission, whereas refractory usually means there was never a period of remission to begin with.

Katherine:                  

Got it. How typical is it for a patient to relapse?

Dr. Kline:       

Well, again, if you look at all comers, if you treated 100 people with DLBCL, most, probably 70 to 75 percent, would go into remission. About 10 or 15 percent would have primary refractory disease and another 10 or 15 percent would have a remission that would end at some point and they would have a relapse. So, it’s not terribly common.

The problem is that once the lymphoma has either demonstrated that it’s refractory to treatment or it’s come back, it’s relapsed, it’s a little bit more difficult to cure the lymphoma at that point.

Katherine:      

How are patients treated then if they’ve relapsed or refractory?

Dr. Kline:       

Well, so for somebody who’s had primary refractory lymphoma or has a lymphoma that’s relapsed after initial therapy, again, say for the sake of argument with R-CHOP, for many, many years, the next line of treatment if you will was to administer what we call salvage chemotherapy, and this is different chemotherapy from the original R-CHOP, that’s meant to put the lymphoma back into remission. In other worse, to salvage a remission. And for folks whose lymphomas were sensitive or responded, shrunk down to that salvage chemotherapy, we would consolidate that remission.

We would make it deeper using high dose chemotherapy and an autologous or a cell, stem cell transplant. And that’s been the standard of care for younger patients for decades.

That paradigm has been challenged, particularly in refractory patients or those who have very early relapses after R-CHOP, by two important clinical trials that have demonstrated superiority of a type of immunotherapy, a cellular immunotherapy called CAR T-cell therapy, which seems to be more effective even than stem cell transplantation in that population of folks.

Prostate Cancer Treatment Tools and Advancements

Prostate Cancer Treatment Tools and Advancements from Patient Empowerment Network on Vimeo.

What’s the latest in prostate cancer treatment tools and advancements? Dr. Heather Cheng from Seattle Cancer Care Alliance shares information about areas of prostate cancer research that have experienced recent advancements.

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Transcript:

Dr. Heather Cheng:

I think it’s a really exciting time. I think there are a lot of advancements throughout prostate cancer. I think one area of importance is early detection, but we also have newer imaging platforms, meaning the way, and we can discover where the prostate cancer is, is advancing through new types of PET scans that we didn’t previously have. And then my own kind of research which is near and dear to my heart is talking about genetics and what we have learned about the genetics of the risk of prostate cancer, but also how the genetics of the cancer itself, which sometimes is inherited, and sometimes isn’t can help us plan for better treatments for patients.

What Treatments Are Available for Non-Small Cell Lung Cancer?

What Treatments Are Available for Non-Small Cell Lung Cancer? from Patient Empowerment Network on Vimeo.

 Dr. David Carbone provides an overview of currently available treatments for non-small cell lung cancer patients, including clinical trials, and reviews factors that influence treatment decisions.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

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Transcript:

Katherine:

What are the current approaches for treating non-small cell lung cancer?  

Dr. Carbone:

Well, that’s a complex question. The basic modalities are surgery, which is really still what we prefer, if we can detect it early; radiation therapy; and medical therapy.  

And medical therapy can be divided into chemotherapies of some sort – what we call targeted therapies, based on genetic abnormalities in the tumor – and then, immunotherapies to harness the immune system to fight cancer. Those are the three major kinds of therapies.  

Katherine:

It seems like patients really do have a lot of options, which is a good thing for them. But how do you then decide which treatment is most appropriate for a given patient? 

Dr. Carbone:

Well, it’s not straightforward. When I started 35 years ago, it really wasn’t clear whether any treatment made any difference, and we actually did a large, randomized trial of doing nothing versus treating, and showed that we could improve survival by a month or two with the currently available treatments. Now, we have a huge toolbox of types of treatments and combinations of treatments. And it really requires a careful analysis of the characteristics of the tumor to pick the best therapy.  

And specifically, for the adenocarcinomas, the most common type, we now do a detailed genetic analysis on all of the tumors, which can completely change the type of treatment people get and the prognosis, and result in being able to match a pill-type targeted therapy to a particular genetic abnormality with really high efficacy and low toxicity. And there are other markers we use for immunotherapy choices. It’s become quite complicated.  

Katherine:

Where do clinical trials fit in, Dr. Carbone?  

Dr. Carbone:

Well, I like to say that clinical trials are tomorrow’s standard of care available today, and all of the new treatments that I’m talking about for lung cancer that have made this dramatic difference in survival and quality of life: They’ve all come because of basic science research, understanding how cancers grow, designing drugs, and using them in people in an intelligent way.  

Historically, we used to just grind up tree bark or dig things up from the bottom of the sea, and test them in tissue culture to see if they killed cancer cells a little more than normal cells. But today, the treatments we have are based on science, and the success of these treatments is very high compared to what they were historically.  

And the way we determine whether a treatment is effective is through something called a clinical trial, where generally the new treatment is compared to the standard treatment.  

And if there is no standard treatment, we still do sometimes use placebo-controlled trials, but often that’s placebo plus some chemotherapy, versus the new drug plus that same chemotherapy.  

So, it’s really not a placebo-only type situation. But the trials are designed to rigorously test whether the drug improves outcomes, and are an extremely important step in developing these new drugs and finding new things to help patients.  

What Is the Difference Between Small Cell and Non-Small Cell Lung Cancer?

What Is the Difference Between Small Cell and Non-Small Cell Lung Cancer? from Patient Empowerment Network on Vimeo.

 Dr. David Carbone discusses the differences between small cell and non-small cell lung cancer. Dr. Carbone then describes the subtypes of non-small cell lung cancer and which types are most common.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

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Transcript:

Katherine:

What is the difference between non-small cell lung cancer and small cell lung cancer?

Dr. Carbone:

Well, I like to tell patients every cancer is different from every other cancer, but they can be broadly categorized in two different categories, small cell and non-small cell.

And this derived from decades ago when small cell lung cancer just looked different under the microscope than non-small cell lung cancer. And different small cells can look different, and now we’re sub-typing small cells. But in general, small cells are treated pretty similarly. Non-small cells are divided into two main groups, the squamous cell carcinomas and the adenocarcinomas.

Adenocarcinomas have a variety of subtypes, as well, and then there are a few of the non-small cell lung cancers that are clearly non-small cell but don’t fit into either of those two categories, and they’re called large-cell or not otherwise specified.

And then, there’s a whole slew of rare types of lung cancers that we probably don’t have time to discuss, and mesothelioma that happened in the chest.

Katherine:

Right. Is one type of lung cancer more common than the other?

Dr. Carbone:

So, the vast majority of lung cancers are the non-small cell lung cancers, about 85 percent. And among the non-small cell lung cancers, most of those are adenocarcinomas or non-squamous. Decades ago, squamous was the most common type, and in some parts of the world, it still is. But in the United States, it depends on the region; 60, 70 percent of lung cancers are adenocarcinomas

Expert Advice for Navigating Non-Small Cell Lung Cancer Care and Treatment

Expert Advice for Navigating Non-Small Cell Lung Cancer Care and Treatment from Patient Empowerment Network on Vimeo.

Dr. David Carbone, a lung cancer specialist, discusses factors to consider when choosing treatment for non-small cell lung cancer (NSCLC). Dr. Carbone provides and overview of the type of treatment for NSCLS, why biomarker testing is essential, and shares advices for playing an active role in your care.

Dr. David Carbone is a medical oncologist and professor of internal medicine at The Ohio State University. Dr. Carbone is also co-leader of the Translational Therapeutics Program at the OSUCCC – James, where serves as director of the Thoracic Oncology Center. Learn more about Dr. Carbone, here.

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Transcript:

Katherine:                  

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss how you can insist on the best care for your non-small cell lung cancer.  

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice.

Please refer to your healthcare team about what might be best for you. All right, let’s meet our guest today. Joining me is Dr. David Carbone. Dr. Carbone, welcome. Would you please introduce yourself?

Dr. Carbone:              

Thank you, Katherine. It’s a pleasure to be here. I’m David Carbone. I’m the director of the thoracic oncology center at Ohio State University in Columbus, Ohio. And I have a 35-year clinical and research interest in lung cancer, and I’m a medical oncologist myself.

Katherine:                  

Excellent, thank you. Thank you for joining us today. Before we get into our discussion, which will focus on non-small cell lung cancer, let’s talk about the types of lung cancer. What is the difference between non-small cell lung cancer and small cell lung cancer?

Dr. Carbone:              

Well, I like to tell patients every cancer is different from every other cancer, but they can be broadly categorized in two different categories, small cell and non-small cell.

And this derived from decades ago when small cell lung cancer just looked different under the microscope than non-small cell lung cancer. And different small cells can look different, and now we’re sub-typing small cells. But in general, small cells are treated pretty similarly. Non-small cells are divided into two main groups, the squamous cell carcinomas and the adenocarcinomas.

Adenocarcinomas have a variety of subtypes, as well, and then there are a few of the non-small cell lung cancers that are clearly non-small cell but don’t fit into either of those two categories, and they’re called large-cell or not otherwise specified.

And then, there’s a whole slew of rare types of lung cancers that we probably don’t have time to discuss, and mesothelioma that happened in the chest.

Katherine:                  

Right. Is one type of lung cancer more common than the other?

Dr. Carbone:              

So, the vast majority of lung cancers are the non-small cell lung cancers, about 85 percent. And among the non-small cell lung cancers, most of those are adenocarcinomas or non-squamous. Decades ago, squamous was the most common type, and in some parts of the world, it still is. But in the United States, it depends on the region; 60, 70 percent of lung cancers are adenocarcinomas.

Katherine:          

Right, okay, that makes sense. I’d like to pivot and talk about treatment for a couple of moments. What are the current approaches for treating non-small cell lung cancer?   

Dr. Carbone:          

Well, that’s a complex question. The basic modalities are surgery, which is really still what we prefer, if we can detect it early; radiation therapy; and medical therapy.

And medical therapy can be divided into chemotherapies of some sort – what we call targeted therapies, based on genetic abnormalities in the tumor – and then, immunotherapies to harness the immune system to fight cancer. Those are the three major kinds of therapies.

Katherine:                  

It seems like patients really do have a lot of options, which is a good thing for them. But how do you then decide which treatment is most appropriate for a given patient?

Dr. Carbone:              

Well, it’s not straightforward. When I started 35 years ago, it really wasn’t clear whether any treatment made any difference, and we actually did a large, randomized trial of doing nothing versus treating, and showed that we could improve survival by a month or two with the currently available treatments. Now, we have a huge toolbox of types of treatments and combinations of treatments. And it really requires a careful analysis of the characteristics of the tumor to pick the best therapy.

And specifically, for the adenocarcinomas, the most common type, we now do a detailed genetic analysis on all of the tumors, which can completely change the type of treatment people get and the prognosis, and result in being able to match a pill-type targeted therapy to a particular genetic abnormality with really high efficacy and low toxicity. And there are other markers we use for immunotherapy choices. It’s become quite complicated.

Katherine:                  

If we’re breaking it down to staging, let’s start with that. What are the stages?

Dr. Carbone:              

Right. So, lung cancer, like many cancers, is staged I, II, III, and  IV, and of course there’s now As, Bs, and Cs, and subcategories of those. But the basic distinction patients need to know has some utility.

So, the stage I lung cancers, in general, are small tumors that aren’t invading into anything, that haven’t spread anywhere to none of the lymph nodes, to no other structures; and they’re the tumors that we like to find. And they’re the ones whose optimal treatment is surgery, with a good cure rate.

Stage IIs, in general, are those lung cancers that are like stage I, except they involve the nearby lymph nodes in the lung that are called hilar lymph nodes, and those have also a high cure rate, but not quite as so high with surgery; and generally, are treated with surgery followed by chemotherapy, and now, immunotherapy.

Stage III is what we call locally advanced. It’s still only in the chest, but it invades some important structure or has multiple lymph nodes that are deep within the chest. And some of these are surgically resectable, but the majority of stage IIIs, I would say, are not surgically resectable, and are treated generally with chemoradiation, again followed by immunotherapy.

With the stage IV lung cancers, really, that is the lung cancer that’s spread outside the chest; typically, to bones, brain, or liver, or elsewhere in the body.

And that is typically not resectable; though again, there’s exceptions to each of these general rules, and you really need to have that multi-disciplinary evaluation of your cancers to determine the best therapy. But in general, stage IV lung cancers are not surgical candidates, not treated upfront as radiation candidates, and they’re generally treated with medical treatments that go throughout the body, and treat spots of cancer wherever they are.

Katherine:                  

How about when we look at general health and comorbidities? How do those influence the treatment choices that you would make?

Dr. Carbone:              

Every patient is different, like every cancer is different, and we have patients who are 20-year-olds and patients who are 90-year-olds; and patients who’ve taken care of themselves, and those that haven’t done so well taking care of themselves.

More than half of patients, even though they used to smoke, are ex-smokers. And so, they generally are in better condition, but we have to take into account frailty and presence or absence of diabetes, kidney disease, and all those other comorbidities, which are common in lung cancer, which has a median age of onset in the upper-60s, where people have these kinds of comorbidities.

We try not to use age alone as a factor, because there are many robust 90-year-olds, and there are many 50-year-olds on oxygen. So, we have to look at the complete picture to plan the best therapy.

Katherine:                  

Yeah. What about treatment side effects? How does that bear on what you decide to treat the non-small cell lung cancer?

Dr. Carbone:    

Well, unfortunately, we don’t cure most lung cancers. And so, our treatments are designed to prolong life and improve quality of life.

So, we’re very aware of the impact of our treatments on the quality of a patient’s life, and we’ve worked hard, over the years, to improve the risk-benefit ratio of our treatments, so to speak. And again, when I started, we didn’t have good nausea medicines, and people got desperately sick to have a six-week prolongation in survival, and that was really of questionable utility.

But now, even the chemotherapies that we give are generally super-well tolerated. The chemotherapies used in lung cancer are often – people will say, “I feel a little tired for a couple of days, but then, I’m fine,” and they’d often continue to work. Most, I would say, have no nausea; they have no significant side effects; and the immunotherapies, on average, people have very few side effects. They can hardly tell they’re getting the treatment, though sometimes the side effects can be significant.

Like everything I’m telling you, there’s always a spectrum.

Katherine:                  

Of course.

Dr. Carbone:              

And the targeted therapies: Again, most often, people have very mild side effects, with maybe a little skin rash or a slight loose stool, or something. But often, it’s insignificant compare to the magnitude of the benefit they get from these treatments.

Katherine:                  

Let’s talk about biomarker testing. What is it, first of all, and what are you looking for, exactly, when you receive the results?

Dr. Carbone:              

Well, you have to order the results, so you have to know what to order. And we already touched on it a little bit. The genetic analysis of a tumor has become central to picking a therapy. And when I say “genetic analysis,” that is what you’re referring to as one of the biomarker tests we use.

Unfortunately, it’s true that many patients have therapies started without waiting for the results of these biomarker tests, and that really can have a negative impact on their care, because the results of this testing can make the difference between chemotherapy or a pill. It’s a totally diametrically different therapy.

So, these genetic tests look for things that we call driver mutations, and these are alterations in the genes of your cancer that are not present in the rest of your body; they’re not passed down to your children, or need to get looked for in your brother or your sister, like some of the breast cancer mutations you may hear about.

These are mutations that are present in the tumor that act like light switches, and they turn the cancer on to grow like crazy.

And through scientific research, we’ve discovered many of these in lung cancer, where, if we can find the specific driver mutation, many of these have specific drugs that can turn that switch back off. And virtually 100 percent or very close to every patient where we can find that matching drug to their driver will have some tumor shrinkage.

And it’s quite remarkable, but we need to do that matching, because these new drugs only work in that subset of patients with that mutation, and that’s why it’s so important to do that matching. And now, we have eight or 10 of these types of mutations that need to be looked for.     

Katherine:                  

Where do clinical trials fit in, Dr. Carbone?

Dr. Carbone:              

Well, I like to say that clinical trials are tomorrow’s standard of care available today, and all of the new treatments that I’m talking about for lung cancer that have made this dramatic difference in survival and quality of life: They’ve all come because of basic science research, understanding how cancers grow, designing drugs, and using them in people in an intelligent way.

Historically, we used to just grind up tree bark or dig things up from the bottom of the sea, and test them in tissue culture to see if they killed cancer cells a little more than normal cells. But today, the treatments we have are based on science, and the success of these treatments is very high compared to what they were historically.

And the way we determine whether a treatment is effective is through something called a clinical trial, where generally the new treatment is compared to the standard treatment.

And if there is no standard treatment, we still do sometimes use placebo-controlled trials, but often that’s placebo plus some chemotherapy, versus the new drug plus that same chemotherapy.

So, it’s really not a placebo-only type situation. But the trials are designed to rigorously test whether the drug improves outcomes, and are an extremely important step in developing these new drugs and finding new things to help patients.

Katherine:                  

A lung cancer diagnosis often has a certain stigma associated with it, but the majority of that is not based in fact. So, I’d like to play a little game with you called Fact or Fiction. All right? All right, first one. Fact or fiction: Lung cancer is a disease of the older population.

Dr. Carbone:              

If you have lungs, you can get lung cancer. That’s it. I’ve seen 20-year-old lung cancer patients. So, I think it can happen to anybody, and unfortunately, things like the CT screening programs are limited to people over the age of 50, but I’ve had many patients in their 30s and 40s. So, if you have lungs, you can have lung cancer.

Katherine:                  

Okay. Next one, fact or fiction: Quality of life is greatly diminished after undergoing treatment for lung cancer.

Dr. Carbone:              

I completely – fiction. I actually tell people often their quality of life is dramatically improved after starting treatments, and that’s my goal.

And with the new treatments, that’s often true. People will tell me within a week that they feel so much better on the treatment than they did before. So, that’s our goal. Our goal is not to make you feel worse. Our goal is to make you feel better.

Katherine:                  

Of course. All right, last one. Fact or fiction: There are no effective treatments for advanced lung cancer.

Dr. Carbone:              

So, the average survival for lung cancer years ago was four to six months from the time of diagnosis to death. That’s bad. And now, we are seeing in these subsets of patients years and years of survival with simple even pill-type treatments or immunotherapies. And even with the immunotherapies, sometimes you get treatments for a year or two, and then we stop; and we have patients who are years later, off of all treatments for metastatic lung cancer, still with no evidence of disease.

So, that is definitely fiction. We have highly-effective treatments for lung cancer. But unfortunately, like everything else, and like I’ve said multiple times, it’s not true for everyone. Our treatments aren’t ideal. Sometimes for a particular patient we can’t find a matching treatment, the standard treatments don’t work, and nothing we can find makes a difference. But I would say you never know that until you try, and for the vast majority of patients, we can definitely give them prolonged, good-quality life. And so, I think that that’s definitely fiction.

Katherine:                  

Okay, thank you. We have received some questions from audience members earlier on.

And so, David writes, “My care team has suggested immunotherapy to treat my lung cancer. I’m optimistic about the results, but nervous about symptoms and side effects. What can I expect?”

Dr. Carbone:              

The immunotherapy is a potent therapy, but you have to understand, you’re dealing with lung cancer, which is a rapidly fatal disease when untreated. So, there’s a balance there. There’s a risk/benefit calculation that happens in picking any treatment.

And it turns out that I would say most lung cancer patients today have immunotherapy as part of their first treatment. Immunotherapy ramps up your own immune system to make it more effective at seeing the cancer, which has previously grown because it’s hidden itself behind a kind of invisibility cloak, and these immunotherapies remove this invisibility cloak so that the immune system can see it.

But at the same time, this process is a normal process that’s used to keep the immune system in check, and keep the immune system from attacking normal tissues, as well. So, it’s pretty common that we see people on immunotherapy have some kind of autoimmune side effect.

The most common side effect with immunotherapy is a skin rash, and usually it’s mild, and you just treat it with a topic corticosteroid, and it’s not a big issue. But it sometimes can be very severe. Like everything else, there’s a spectrum. I would say most patients have no skin problems; some have severe; and it’s almost always treatable. The next most common side effect is thyroid endocrine disorders. So, people will get thyroid function loss. And so, this is something that we follow carefully in the clinic, and people who are on immunotherapy.

And when we start seeing their thyroid levels going down, we just start them on thyroid medication, and that completely fixes that problem. So, but it’s usually permanent, and even after they stop immunotherapy, they’ll need to take thyroid medicines and adjust their thyroid levels.

And then, there’s a whole slew of other possible side effects that are less common. Some are very severe. Less than one percent of patients have a severe side effect called colitis, which causes diarrhea, which can even be life-threatening, but is also treatable if detected early. Very uncommon to be so severe, but patients should let their doctors know if they experience unusual diarrhea.

You can also have inflammation in your lungs called pneumonitis. So, if there’s an onset of shortness of breath, of course, you’ll tell your doctor, and that can be treated, as well. And anything else, there’s a huge list of other things. Arthritis, uveitis, other things that happen, but are pretty rare.

Katherine:                  

Lindsay sent in this question: “My doctor has talked about putting me on maintenance therapy following my treatment regimen. What is maintenance therapy for lung cancer?”

Dr. Carbone:              

So, many of our treatments have a maintenance phase, and I’m not sure which treatment she’s talking about. But even with chemotherapy, now, if people are on chemotherapy alone, will usually use a double chemotherapy to start, and then will drop one of the chemos after a few cycles, and then continue the other as a maintenance.

A more typical regimen today is a combination of two chemos and an immunotherapy. And generally, we’ll stop the more toxic chemotherapy after a few cycles and continue the less toxic chemotherapy plus the immunotherapy, usually for up to two years.

After chemo-radiation, you’d have a maintenance immunotherapy as well. So, maintenance therapy is just a lower-intensity therapy after your initial therapy, designed to keep the cancer from coming back.

Katherine:                  

Right. Okay. We have one other question, this one from Shelley: “Is lung cancer hereditary? I’m curious if my children should undergo genetic counseling, since I was diagnosed with lung cancer.”

Dr. Carbone:             

Well, that’s a simple, complicated question.                                   

So, in general, lung cancer is not hereditary. It’s not like familial breast cancer or ovarian cancer, or those kinds of cancers, or retinoblastoma. Most cases of lung cancer are caused by environmental exposure to cigarette-smoking or radon, and are not passed on to your kids genetically, though there is shared exposure, right?

There are some really rare genetic predispositions that we sometimes find on these biomarker panels.

But the vast, vast majority of lung cancers are not heritable, and you don’t need to worry about your kids, except to tell them not to smoke, and test for radon.

Katherine:                  

Patients can sometimes feel like they’re bothering their healthcare team with their comments and questions. Why is it important for patients to speak up, and become a partner in their own care?

Dr. Carbone:              

So, it’s a fact that when patients get the diagnosis of lung cancer, everything changes in their lives. They suddenly have a whole new vocabulary thrown at them. It’s like their doctor is speaking French to them. They have to trust their life to a person they’ve never met before, and a whole cadre of people coming in and talking to them and poking them and running through scanners.

It’s very difficult for someone whose biggest concern was what to make for dinner that night, and now has a diagnosis of lung cancer, to really comprehend what’s going on. And lung cancer is complicated, so I recommend that patients really try their best to have at least a basic understanding of what’s going on, where their cancer is. I always show the patient their scans.

“Your cancer is here; this is what it looks like; that’s why you’re having that pain over there, because you have this spot here. Your genetic testing shows this and this, and that’s why it’s important, and that’s why we’re using this drug to match this mutation.” And these are things patients will understand if doctors will explain it to them.

And similarly, the side effects. Lung cancer patients tend to be tough people. They’ll say, “It’s not so bad, I feel better; but the side effect is not so bad. I’m just not going to tell them.” And it even happens in clinic that they’ll tell me they feel fine, and then they’ll tell the nurse that they hurt in their left elbow. And I have to go back in and ask them some more questions on that.

So, it’s extremely important to feel comfortable in communicating with your doctor, asking questions; “Why am I getting this scan? Why are we using this treatment? Is this the best treatment? Are there clinical trials available? I have this new symptom, x, y, z,” because symptoms are often much easier to treat when you catch them early than when you catch them late.

And you don’t get a medal for being a tough guy in this situation. Tell your doctor if you have pain, and they can manage it. Tell them if you’re short of breath, and they can help you feel better. They can’t help you if you don’t tell them, and you are your own best advocate in this situation. Ask questions about the treatment, and why that’s the best one for you; and, as I said, about clinical trials.

Katherine:

Excellent. Thank you so much. It’s important for people to remember that.                   

And I just want to remind our audience that you can send in your questions to question@powerfulpatients.org, and we’ll get them answered, hopefully, on future programs.

So, Dr. Carbone, just to wrap things up, what are you excited about in lung cancer research right now, and what would you like to leave the audience with?

Dr. Carbone:              

Well, there’s a lot to be excited about in lung cancer right now. There’s new therapies being approved all the time. We have more new approvals in the last few years than in the last few decades put together. So, there’s a lot to be excited about.

But there’s still a lot of room for improvement, and there are a lot of patients who still suffer and die from lung cancer. So, my message to patients would be to make sure they get their biomarker testing before they start treatment. And it doesn’t mean to get the tests sent off and start on Joe Random treatment, until the test comes back. This means wait until the test comes back before starting treatment.

And then, I would recommend getting second opinions, if a patient is in a private practice without availability of clinical trials, to investigate if there might be new clinical trials available for them; again, before starting treatment, because sometimes even that first dose of standard chemo may make you ineligible for a trial. So, No. 1 is biomarkers.

Katherine:                  

All right. Thank you so much for joining us today.

Dr. Carbone:              

Well, you’re very welcome. Thank you for helping patients better understand how to deal with this disease.

Katherine:                  

And thank you to all of our partners.

To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.

Questions to Ask Your Doctor About Essential Myeloma Testing

Questions to Ask Your Doctor About Essential Myeloma Testing from Patient Empowerment Network on Vimeo.

Being empowered to speak up about your myeloma care is not only important but essential. Dr. Saad Usmani, a myeloma expert, shares advice for partnering with your doctor and provides key questions to ask about myeloma test results.

Dr. Saad Usmani is the Chief of Myeloma Service at Memorial Sloan Kettering Cancer Center in New York City. Learn more about Dr. Usmani, here.

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Transcript:

Katherine Banwell:

If patients are concerned about voicing their concerns and I think many of us are, why should they feel like they’re a partner in their care?

Dr. Usmani:

Well, that’s the only way that they will feel empowered. And we have to remember why we’re doing this, right? So, we’re doing this so that we can alleviate the burden of this disease from our patients and give them as good of quality of life as possible. And it’s a partnership. And in that partnership, the patient is the most important partner. Everyone else – it’s like you’re the main character.

The patient’s the main character in the movie. And all of us are supporting cast around them. I think that’s how you have to approach it. That’s how – that’s why it’s very important. And of course, patients – we’re not expecting our patients to read the papers and be knowledgeable about everything. But have a general sense of what to expect and it will be – so, having a more educated patient helps them deal with treatments better and have realistic expectations of what’s to come.

Katherine Banwell:

Right. As I mentioned at the start of this program, Dr. Usmani, patients should insist on essential myeloma testing prior to choosing a treatment. As we conclude, I think it’s important to point out that some patients may not know if that can even receive these important tests. So, what key question should they ask their physician about them?

Dr. Usmani:

So, you should be asking your physician about what kind of myeloma you have? What stage of myeloma you have? How much involvement in the bones you have? Do you have any chromosome abnormalities or any features of disease that put you at a higher chance of the myeloma coming back?

As you ask these questions, your physician will be prompted to think about “Okay. Am I missing something in my work?” And you can always ask is there anything else you need to do in terms of testing to give you a better idea of how best to approach my treatment and follow-up.