How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last? from Patient Empowerment Network on Vimeo.

Dr. Joshua Richter, a myeloma specialist, reviews the goals of maintenance therapy and discusses the timeline for this type of treatment.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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What Myeloma Patients Should Know About Treatment Monitoring


Transcript:

Katherine:

Isaac sent us this question. How long does the average myeloma patient remain on Revlimid? And is there a suggested time period? 

Dr. Richter:

Really great question. It depends upon the setting we’re looking at, and for the most part, a lot of people are probably asking about the maintenance setting. So, after initial therapy or after transplant, we put you on Revlimid. How long do we keep you on? The American adage has always been, “More is better,” so as long as you tolerate it and as long as it works. Outside of the U.S., they’ve done a couple of studies looking at one year and then stopping, or two years and then stopping.  

And in a big trial that got presented a year or so ago, they compared the two years then stopping versus just staying on, and the people who just stay on do better.  

So, now the current thinking is just keep you on long-term. What’s going to change that in the long term is we’re starting to use a technology called MRD, minimal residual disease, so, doing a marrow and trying to find one in a million or one in 10 million cancer cells.   

And then, there’s something called sustained MRD meaning if you do two MRD analyses at least 12 months apart and they’re both negative, we call that sustained MRD-negative.   

And, there’s a hint that some people on maintenance Revlimid who have sustained their MRD negativity, they may do just as well stopping versus staying on it. We don’t know exactly who that is yet, but that’s going to be better understood in the next few years.  

What Myeloma Patients Should Know About Treatment Monitoring

What Myeloma Patients Should Know About Treatment Monitoring from Patient Empowerment Network on Vimeo.

How do you know if your myeloma treatment is working? Dr. Joshua Richter, a myeloma specialist, reviews how treatment response is measured in myeloma and why it’s important to share any symptoms or side effects with the healthcare team.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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Is It Too Late for a Myeloma Second Opinion?

Is It Too Late for a Myeloma Second Opinion?

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What Are Common Myeloma Treatment Side Effects?

How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last?


Transcript:

Katherine:

So, once treatment has begun, how do you know if it’s working? 

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.  

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.  

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.  

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow. 

Katherine:

All right. How do you know when it’s time to switch treatment? 

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.  

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.  

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down. 

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?  

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”  

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.  

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.  

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid.  

So, really any time something changes.  

How Can Myeloma Treatment Impact Kidney Health?

How Can Myeloma Treatment Impact Kidney Health? from Patient Empowerment Network on Vimeo.

Dr. Joshua Richter discusses the impact of myeloma treatment on the kidneys and provides key advice for optimal kidney health.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last?


Transcript:

Katherine:

Are kidneys impacted by any of the medications that patients take? 

Dr. Richter:

So, kidneys are an excruciatingly important part of myeloma, and in my mind, one of the keys to long-term survival and outcome. So, there are three things that I tell all of my patients to help preserve long-term kidney health. Two of them are easy to wrap the head around. One is a little bit harder. Number one, keep yourself well hydrated. The kidneys are like a filter. Think, like, the filter for your car. If you drove 100,000 miles in the desert and didn’t change your oil, there’d be problems. So, especially now that there’s warmer weather, by the time you already feel yourself dehydrated, you’re about 10 to 15 percent low on the total amount of body water you need.  

So, especially if you’re going out there doing yard work, playing with the kids or grandkids, make sure you’re drinking plenty of water. Two, avoid NSAIDs. Drugs like Aleve, or naproxen, or Advil, or ibuprofen can be harmful to the kidneys. So again, please discuss with your care team. There may be better alternatives to treat your pain without hurting the kidneys. And the third is when all else possible, avoid intravenous contrasts for CAT scans. Now, the IV contrast you get for MRIs is called gadolinium. It’s not harmful to the kidneys. But the contrast for CAT scans is iodine-based, and although the newer formulations are better, it can still hurt the kidneys.   

So, my advice is the following. If you’re in the ER at 2:00 a.m. in the morning and they want to do an urgent CAT scan with IV contrast, let them do it. It’s likely not going to be an issue. If you go to see an orthopedist and they say, “I want to get a better look at that leg that’s bothering you. I’m going to get a CAT scan with IV contrast,” tell them to call me. We’ll find an alternative. 

What Are Common Myeloma Treatment Side Effects?

What Are Common Myeloma Treatment Side Effects? from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Joshua Richter reviews common side effects of myeloma treatment and strategies for managing them. 

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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How Long Will Myeloma Maintenance Therapy Last?


Transcript:

Katherine:

Can you help us understand some of the common issues that myeloma patients experience and how they might be managed? 

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.  

And I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy, and they may be using drugs like gabapentin or Lyrica.  

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And many of these drugs may be used for anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.  

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions from Patient Empowerment Network on Vimeo.

Treatment for myeloma varies from one patient to the next. Dr. Joshua Richter, a myeloma specialist, reviews the factors that are considered when choosing a treatment approach.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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How to Thrive and Set Myeloma Treatment Goals

How to Thrive and Set Myeloma Treatment Goals

What Are Relapsed and Refractory Myeloma?

What Are Relapsed and Refractory Myeloma?

What Are Common Myeloma Treatment Side Effects?

What Are Common Myeloma Treatment Side Effects?


Transcript:

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient? 

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro, and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).  

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?  

So, those are some of the big factors. And then, treatment related factors. Have you had certain other drugs? So, if you’re refractory to Revlimid, I may not want to give you Revlimid again. 

If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like Pomalyst.  

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline. 

What Are Relapsed and Refractory Myeloma?

What Are Relapsed and Refractory Myeloma? from Patient Empowerment Network on Vimeo.

Dr. Joshua Richter, a myeloma specialist, explains what it means to have relapsed myeloma or refractory myeloma.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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How to Thrive and Set Myeloma Treatment Goals

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What Are Common Myeloma Treatment Side Effects?


Transcript:

Katherine:

Let’s define a couple of terms that are often mentioned in myeloma care. What does it mean to be refractory, and how is that different from relapsing? 

Dr. Richter:

Great question. So, these terms have very specific definitions in myeloma. “Relapsing” just means that the disease is coming back. So, you had myeloma that was measurable, you went into a remission, and now it is showing signs that it’s coming back. We call that “relapsing.” And depending upon what type of myeloma, we have specific definitions. So, if you’re IgG kappa and you make an M-spike, if your M-spike goes up at least 0.5 and at least 25 percent, we call that “relapsing.” If you’re a light chain, it’s gotta go up by at least 100. But you’ve got to make sure the units are right.  

“Refractory” means that you either did not respond or you’re progressing on or within 60 days of your last treatment.  

So, I put you on Revlimid maintenance, and you’re on Revlimid, and your disease gets worse. You are now relapsed and refractory to Revlimid. If I give you a transplant and then I put you on nothing, and two years later your disease comes back, you’re relapsed but not refractory.  

How to Thrive and Set Myeloma Treatment Goals

How to Thrive and Set Myeloma Treatment Goals from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Joshua Richter discusses the benefit of setting myeloma treatment goals with your healthcare team.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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Defining the Myeloma Patient Role in Their Care

Defining the Myeloma Patient Role in Their Care

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Key Factors That Guide Myeloma Treatment Decisions

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What Are Common Myeloma Treatment Side Effects?


Transcript:

Katherine:

Excellent. Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with myeloma.

Dr. Richter:

Absolutely. And I love that term. I recently chaired a 5K walk for the MMRF, and the word that is thrown around a lot in cancer is “survivorship.” And, I got up there and I said, “That’s not a word I like to use. I like to use the word “thrivorship.” So, I love that you’re using this word because to me, surviving is an important part of dealing with cancer, but it’s the first step. Thriving is the goal. The goal is not to just get through it. It’s to go beyond it. It’s to do everything you want to do in life: personal, family, business, anything you want.

If you want to spend your time fishing, if you want to spend your time skydiving, if you want to spend time with your grandkids, and enjoying that time, and as much as humanly possible, keeping the notion of cancer way out of your brain. To me, that is thriving and not just surviving with a diagnosis like myeloma.

Katherine:

That helps us guide through the conversation as we continue on. Getting the appropriate myeloma care is, of course, part of thriving. So, let’s talk about treatment. How would you define treatment goals?

Dr. Richter:

Sure. So, treatment goals are different for each different individual because unfortunately, myeloma tends to affect people who are older. So, whereas the goals for an 85 or 90-year-old diagnosed with the disease is maybe things like, “I don’t want to suffer. I don’t want to have as many side effects,” but the goal is not to live 40 years, that’s different from a 40-year-old who may say, “I’m willing to tolerate certain side effects because I want to live as far as possible.” So, in reality, there always has to be this huge balance. And as with anything in medicine, an open dialogue with your care team is crucial to understand what your goals are because a lot of us make assumptions on both sides.

The patient may assume that we want certain things out of this. We may assume the patient wants certain goals. Really open, vibrant discussions where there are no taboos, there’s nothing wrong to say. I’ve had patients say, “I don’t care what happens. My granddaughter is getting married next year. I need to be there.

Anything beyond that, I don’t care.” That’s their goal. They’re entitled to their goal. I will work with them within that construct. So, really being open about what the goals are. Right now, what I tell patients is, especially for younger patients who if you’re already 85 or 90, you’re getting closer and closer to how long you’re likely to survive even without myeloma.

It’s kind of hard to have a 90-year-old have a 30-year survival. We’re not living to 120 just yet anyway. But for most of my patients, I say my goal is to either keep you in remission so long that you pass from something else many years from now, or to keep you moving until we have a cure that we can just give you and then make sure that that cure, that you’re able to accept it. That your body’s intact, your bone marrow’s contact, and this is something we can provide for you.

Myeloma Research | CAR-T Cell & Bispecifics Study Updates

Myeloma Research | CAR-T Cell & Bispecifics Study Updates from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Joshua Richter reviews the latest updates in myeloma research from the 2022 American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) Congress.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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What Myeloma Patients Should Know About Treatment Monitoring

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021


Transcript:

Katherine:

There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

What makes you hopeful? 

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.  

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.  

We are at the precipice of a brand-new Gestalt switch in myeloma. The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR-Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.  

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.  

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.  

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”   

And with so many great partners between advocacy groups and pharma and patients and cancer centers, we’re going to collaborate, and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.   

Katherine:

Oh, I bet. I bet. 

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses highlights from the recent American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) 2022 Congress. Dr. Patel shares promising research updates related to approaches including: stem cell transplant, CAR T-cell therapy, and bispecifics.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

What Is Myeloma CAR T-Cell Therapy?

Immunotherapy: Which Myeloma Patients Is It Right For?

Transcript:

Katherine:   

Dr. Patel, cancer researchers recently came together at the annual ASCO and EHA meetings. Are there any highlights from the meetings that myeloma patients should know about?

Dr. Patel:    

Yeah, so we had some amazing trials that were presented at both. And I got to actually go to Chicago for the ASCO meeting, and I’ll say we actually had a plenary session that was presented for myeloma. That doesn’t happen as often as we like. So, basically that was a study presented by Dana-Farber and all of the different groups around the U.S. that did a transplant study. And basically, they’re looking at patients who got induction therapy when they’re newly diagnosed with transplant versus they didn’t get transplant upfront. And it’s called the determination study, and it was to determine should everybody be getting a stem cell transplant.

Katherine:  

Right.

Dr. Patel:   

And this is a trial that’s been going on for over 10 years; that’s why it was so highly anticipated. And basically, the biggest thing that we saw was what we call progression-free survival; so, the time that the myeloma hibernates is what I call it, for PFS. Basically, patients who got transplant upfront, it was 21 months longer that it stayed hibernating than if you didn’t get transplant upfront. So, that’s the trial, that’s what it was looking at, and that’s all they could really say about it. The good news is, even patients who didn’t get transplant upfront but then got transplant in second remission tended to have a really good, long progression-free survival or hibernation in that second remission.

So, it still tells us that right now, a transplant is still important for the majority of our myeloma patients. And basically, that’s sort of what that trial showed.

Now, the difference is we do different types of upfront therapies and we have new things like CAR T and bispecifics that are coming up earlier. So, we’ll see in the future if it still holds up. But as of right now, it still holds up for transplant. The other big studies, of course, were some of our bispecific studies that use different antigens. So, antigens are the flags that are on the myeloma that we make these receptors for CAR T, so they can find the myeloma, or bispecifics go after that.

And basically, there are other antigens. BCMA, B-cell maturation antigen, is the big one that we use for everything right now. But now, we found even more antigens, which is fantastic.

So, we have something called FcHR5. We have something called GPRC5D. It’s like alphabet number soup, basically. But what’s really exciting is that these new antigens give us a different way of getting to that myeloma, especially if someone has already had a BCMA therapy and they’ve relapsed on that. Well, now we have even new ways to get to that myeloma cell. So, I think that’s some really, really exciting data.

And then, I’ll say the other big one was one of the CAR Ts, Cilta-Cel was something that they presented.

Again, this was two years after the last patient had gotten treated on the trial. And so far, they still have about 71 percent of patients that are still in remission two years after. So, that is huge.

Katherine:                  

Wow.

Dr. Patel:  

We’ve never seen that in relapsed refractory patients before, so we’re really, really excited to kind of have gotten that data to say, “Okay, we found a brand-new way of treating myeloma.” And it really is changing how we’re looking at even earlier lines of therapy now.

Katherine:   

Such promising news. That’s great.

What Are the Side Effects of Myeloma Immunotherapy?

What Are the Side Effects of Myeloma Immunotherapy? from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses the common side effects of immunotherapy and reviews tools that may be used to prevent complications.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

What Is Myeloma CAR T-Cell Therapy?

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

Are there other side effects that patients should know about and side effects that they might experience?

Dr. Patel:  

Yeah, so neurotoxicity is one that we don’t see as much as we see in lymphoma patients, which is again great but sometimes people can get something called ICANS, which is a type of neurotoxicity in the first 30 days after CAR T.

And basically, it can be as bad as seizures, but thankfully we don’t see that very often, or I haven’t seen it at all. But it can cause confusion. It can cause people to be extra sleepy. So, we have different treatments that we give to turn that around. Longer term, really, the big side effects are the counts being low. So, what we call cytopenias. So, white count, hemoglobin, platelets.

And so, that is something we see quite often in our patients who have had a lot of therapy for myeloma already, and then are getting something like CAR T.

So, a lot of my patients will still need transfusions even a month or two or three after, and we’re giving GCSF to help their white count come back up, et cetera.

Katherine:    

What’s that?

Dr. Patel: 

So, G-CSF is basically a growth factor that helps your neutrophil; so, a different type of white blood cell – come back up, which helps fight against bacterial infections.

So, it’s the same medicine for anyone who’s had a stem cell transplant. It’s the same medicine you get to get your stem cells into your blood but it’s at a lower dose. But again, it’s to avoid infections, to help present bacterial infections. The other one is infections can also be caused because of low IgG levels or what we call immunoglobulins; these are our antibodies that we have.

And the good news is, when CAR Ts or bispecifics or some of these immune therapies work really well, they’ll kill as many myeloma cells as we possibly can.

But they also kill good cells. So, they kill good plasma cells that make us antibodies and good B cells that make us antibodies. So, when that happens, people’s IgG levels will go down and that puts you at risk for infection too. So, we actually aggressively give people IVIG to help prevent those infections.

Immunotherapy: Which Myeloma Patients Is It Right For?

Immunotherapy: Which Myeloma Patients Is It Right For? from Patient Empowerment Network on Vimeo.

Dr. Krina Patel, a myeloma specialist and researcher, explains how newer therapies, such as CAR T-cell therapy, are being used in myeloma and which patients these treatments are most appropriate for.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

What Are the Side Effects of Myeloma Immunotherapy?

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

Now, in reference to immunotherapy and CAR T-cell therapy, who are these types of treatments right for?

Dr. Patel:    

So, I think it’s really exciting that we finally are getting standard of care therapies for all these new immune therapies. So, our first CAR T for myeloma got approved a little over a year ago. Our second CAR T got approved just a couple of months ago, and we’re hoping our first bispecific will be approved in just a couple months.

Our fingers crossed. On the clinical trials, I will say our patients who had a good performance status, meaning they’re able to do everything else normally life-wise, those are the patients that got onto those clinical trials; and the reason is safety-wise.

So, T cells when we use them to kill myeloma, they release cytokines or enzymes, you can say, that are inside the T cells and that’s what they use to communicate with other immune cells to come help them kill.

Those are the same cytokines that make people feel really ill when they have the flu, for instance. So, as our immune system tries to fight infections when people get fevers, they feel chills, they feel just fatigued and tired, it’s those same kind of cytokines that, even when you try to kill the myeloma with T cells, people can get that same type of symptoms.

And really, the main, fevers and things like that, we can take care of. But when patients’ blood pressure drops or if their oxygen levels drop really low, that’s where we can run into some trouble. Now, the good news is, in myeloma, most of these new therapies don’t cause really bad CRS [Cytokine Release Syndrome] or really bad neurotoxicity that we can sometimes see. And so, thankfully most patients are okay, but really it’s making sure that none of our patients have bad toxicity. So, most of our myeloma patients, I will say, are eligible for these therapies. However, if someone has really bad heart disease or really bad lung disease, those are patients that maybe these are not the right therapies for.

What Is Myeloma CAR T-Cell Therapy?

What Is Myeloma CAR T-Cell Therapy? from Patient Empowerment Network on Vimeo.

How does CAR (chimeric antigen receptor) T-cell therapy work to fight myeloma? Dr. Krina Patel, a myeloma specialist and researcher, explains how this novel therapy uses your immune system to treat the disease.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

Immunotherapy: Which Myeloma Patients Is It Right For?

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

What is CAR T-cell therapy?

Dr. Patel:    

So, CAR-T cells are sort of a biologic immune therapy where we are able to take T cells, a type of lymphocyte which help us, normally. All of us have them in our blood.

They come from our bone marrow, go into our blood, and they sort of go around in the blood and look for bad things, pathogens. So, infections, even cancer cells, our T cells help get rid of all of those bad things that we’re not supposed to have. And they each have a receptor. And so, T cells have this night vision, and they’re made for a specific type of pathogen out there that we aren’t supposed to have that can hurt us.

And so, what we can is to either take your own T cells out, or sometimes with something called allo CAR-T use a normal donor’s T cells. And when we take them, we basically can put a new receptor in there, a new night vision; and so, now they are trained to go after something that’s specific on the myeloma instead of a bacteria or a virus or anything. And basically, we grow those cells, and then we give those cells back to our patient after a low dose of chemotherapy, just so these T cells can go in, find the myeloma, use that night vision to find that myeloma wherever it is, kill, and then it actually causes other immune cells in your system to come there and start helping to kill as well.

And then, they start coming back down again. And so, really, it’s a novel way of using your own immune system, or somebody else’s, but to actually enhance both by the target to get that myeloma precisely as well as making more of them so that there’s enough to go around and kill all the cells that we possibly can.

How Does Immunotherapy Treat Myeloma?

How Does Immunotherapy Treat Myeloma? from Patient Empowerment Network on Vimeo.

Immunotherapy harnesses one’s own immune system to fight cancer. Dr. Krina Patel, a myeloma specialist and researcher, explains how this therapy changing the treatment landscape for myeloma.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

What Is Myeloma CAR T-Cell Therapy?

Immunotherapy: Which Myeloma Patients Is It Right For?

What Are the Side Effects of Myeloma Immunotherapy?

Transcript:

Katherine:   

We’ve been hearing a lot recently about immunotherapy. Would you tell us what it is and how it works to treat myeloma?

Dr. Patel:       

Yeah, so I think immunotherapy is sort of where everything is  really changing the way we look at myeloma. So, I’ll date myself a little bit, but 15 years ago when I was a first-year fellow most people thought that immunotherapy wouldn’t necessarily work for myeloma. So, in all cancer care we have surgery possibly in myeloma.

We don’t use it as much, but if someone has a bone lesion that we need to do we might do some surgery there. We use radiation sometimes if we really need, for painful lesions or something that might be at risk for fracture. And we use chemotherapy all the time for treatment.

Immunotherapy is actually different types of medications. Some are proteins. Some are biologics that we can talk about it. But really, they harness your immune cells, all the other white blood cells that are in your bone marrow and in your blood, to actually go after the myeloma themselves. And so, there’s different ways we can do that. And, again, 15 years ago most people said, “No, we’re not going to be able to use immune therapy for myeloma because plasma cells,” which are myeloma cells, “are a white blood cell. So, their sisters, brothers, cousins, whatever you want to call those other white blood cells, how do we turn those into the enemy, or how do we make myeloma the enemy?”

And so, it took a long time for us to figure it out, but really, it’s about using your immune cells to kill that myeloma.

Thriving with Myeloma: What You Should Know About Care and Treatment

Thriving with Myeloma: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with myeloma? Myeloma specialist and researcher, Dr. Joshua Richter discusses the goals of myeloma care, reviews treatment options –including research updates – and shares tools for taking an active role in decisions.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

Download Guide

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Updates in CAR T-Cell Therapy for Myeloma from ASH 2021


Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is about how to live and thrive with myeloma. We’re going to discuss myeloma treatment goals and how you can play an active role in your care. Before we meet our guest, let’s review a few important details. 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. Joshua Richter. Dr. Richter, welcome. Would you please introduce yourself?

Dr. Richter:

Hi. Thank you for having me today. My name is Joshua Richter.

I’m an associate professor of medicine at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai and the director of myeloma at the Blavatnik Family Chelsea Medical Center of Mount Sinai.

Katherine:

Great. Thank you for taking the time to join us today. There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

Excellent. Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with myeloma.

Dr. Richter:

Absolutely. And I love that term. I recently chaired a 5K walk for the MMRF, and the word that is thrown around a lot in cancer is “survivorship.” And, I got up there and I said, “That’s not a word I like to use. I like to use the word “thrivorship.” So, I love that you’re using this word because to me, surviving is an important part of dealing with cancer, but it’s the first step. Thriving is the goal. The goal is not to just get through it. It’s to go beyond it. It’s to do everything you want to do in life: personal, family, business, anything you want.

If you want to spend your time fishing, if you want to spend your time skydiving, if you want to spend time with your grandkids, and enjoying that time, and as much as humanly possible, keeping the notion of cancer way out of your brain. To me, that is thriving and not just surviving with a diagnosis like myeloma.

Katherine:

That helps us guide through the conversation as we continue on. Getting the appropriate myeloma care is, of course, part of thriving. So, let’s talk about treatment. How would you define treatment goals?

Dr. Richter:

Sure. So, treatment goals are different for each different individual because unfortunately, myeloma tends to affect people who are older. So, whereas the goals for an 85 or 90-year-old diagnosed with the disease is maybe things like, “I don’t want to suffer. I don’t want to have as many side effects,” but the goal is not to live 40 years, that’s different from a 40-year-old who may say, “I’m willing to tolerate certain side effects because I want to live as far as possible.” So, in reality, there always has to be this huge balance. And as with anything in medicine, an open dialogue with your care team is crucial to understand what your goals are because a lot of us make assumptions on both sides.

The patient may assume that we want certain things out of this. We may assume the patient wants certain goals. Really open, vibrant discussions where there are no taboos, there’s nothing wrong to say. I’ve had patients say, “I don’t care what happens. My granddaughter is getting married next year. I need to be there.

Anything beyond that, I don’t care.” That’s their goal. They’re entitled to their goal. I will work with them within that construct. So, really being open about what the goals are. Right now, what I tell patients is, especially for younger patients who if you’re already 85 or 90, you’re getting closer and closer to how long you’re likely to survive even without myeloma.

It’s kind of hard to have a 90-year-old have a 30-year survival. We’re not living to 120 just yet anyway. But for most of my patients, I say my goal is to either keep you in remission so long that you pass from something else many years from now, or to keep you moving until we have a cure that we can just give you and then make sure that that cure, that you’re able to accept it. That your body’s intact, your bone marrow’s contact, and this is something we can provide for you.

Katherine:

Well, tell me what you think the patient’s role is, then, in setting care goals.

Dr. Richter:

Absolutely. The patient has the most crucial role of course. And, one of the things is honesty and really being to a point of brutal honesty with how they’re doing. I always tell patients, “You don’t get extra points for suffering. It’s not that if you sit there in pain you’re going to do better. Let me know what type of pain you’re having.” And pain doesn’t just mean a bone is hurting, or a muscle’s hurting, we call somatic pain.

There can be neuropathic pain where the nerves hurt.

There can be emotional and spiritual pain. These things all need to be addressed. And if you are suffering in silence, we have a lot of tools nowadays not just medicines. We have people to talk to. We have resources. So, letting us in to help is one of the most crucial things because we’ve actually shown that if you actually improve some of these, you may actually improve overall outcomes. So, the patient, please, all we want to do on the care side of the equation is help.

Let us know what’s bothering you. It may be small to you, it may be big to us, or vice versa, but the more open you are, the better we can help.

Katherine:

Yeah, that’s great advice. Before we move on to discussing how the treatment choice is determined, let’s define a couple of terms that are often mentioned in myeloma care. What does it mean to be refractory and how is that different from relapsing?

Dr. Richter:

Great question. So, these terms have very specific definitions in myeloma. “Relapsing” just means that the disease is coming back. So, you had myeloma that was measurable, you went into a remission, and now it is showing signs that it’s coming back. We call that “relapsing.” And depending upon what type of myeloma, we have specific definitions. So, if you’re IgG kappa and you make an M-spike, if your M-spike goes up at least 0.5 and at least 25 percent, we call that “relapsing.” If you’re a light chain, it’s gotta go up by at least 100. But, you’ve gotta make sure the units are right.

“Refractory” means that you either did not respond or you’re progressing on or within 60 days of your last treatment. So, I put you on Revlimid maintenance, and you’re on Revlimid, and your disease gets worse. You are now relapsed and refractory to Revlimid. If I give you a transplant and then I put you on nothing, and two years later your disease comes back, you’re relapsed but not refractory.

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient?

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?

So, those are some of the big factors. And then, treatment related factors. Have you had certain other drugs? So, if you’re refractory to Revlimid, I may not want to give you Revlimid again. If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like Pomalyst.

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline.

Katherine:

Right. Can you help us understand some of the common issues that myeloma patients experience and how they might be managed?

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.

And, I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy and they may be using drugs like gabapentin or Lyrica.

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And, many of these drugs may be used for

anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.

Katherine:

Are kidneys impacted by any of the medications that patients take?

Dr. Richter:

So, kidneys are an excruciatingly important part of myeloma, and d in my mind, one of the keys to long-term survival and outcome. So, there are three things that I tell all of my patients to help preserve long-term kidney health. Two of them are easy to wrap the head around. One is a little bit harder. Number one, keep yourself well hydrated. The kidneys are like a filter. Think, like, the filter for your car. If you drove 100,000 miles in the desert and didn’t change your oil, there’d be problems. So, especially now that there’s warmer weather, by the time you already feel yourself dehydrated, you’re about 10 to 15 percent low on the total amount of body water you need.

So, especially if you’re going out there doing yard work, playing with the kids or grandkids, make sure you’re drinking plenty of water. Two, avoid NSAIDs. Drugs like Aleve, or naproxen, or Advil, or ibuprofen can be harmful to the kidneys. So again, please discuss with your care team. There may be better alternatives to treat your pain without hurting the kidneys. And the third is when all else possible, and avoid intravenous contrasts for CAT scans. Now, the IV contrast you get for MRIs is called gadolinium. It’s not harmful to the kidneys. But, the contrast for CAT scans is iodine-based, and although the newer formulations are better, it can still hurt the kidneys.

So, my advice is the following. If you’re in the ER at 2:00 a.m. in the morning and they want to do an urgent CAT scan with IV contrast, let them do it. It’s likely not going to be an issue. If you go to see an orthopedist and they say, “I want to get a better look at that leg that’s bothering you. I’m going to get a CAT scan with IV contrast,” tell them to call me. We’ll find an alternative.

Katherine:

Okay. All right. Good advice. Thank you. So, once treatment has begun, how do you know if it’s working?

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow.

Katherine:

All right. How do you know when it’s time to switch treatment?

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down.

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid. So, really any time something changes.

Katherine:

Anything. Yeah. I want to make sure that we get to some of the audience questions. So, let’s start with this one. PEN community member Sal sent in this question prior to the program. “What is the difference between myeloma and multiple myeloma?”

Dr. Richter:

A really great question. For the most part, the terms are synonymous. We abbreviate multiple myeloma as myeloma. But along those lines, and I literally saw a patient today who said, “Why is it called multiple myeloma?” Well, when you have a group of bad plasma cells that forms a tumor, we call that a plasmacytoma, “cytoma” meaning “bad cells,” and “plasma” because they’re plasma cells. And when you have one of them, it is a solitary plasmacytoma. Once you have two of them, it’s multiple myeloma because it’s in multiple spots in the marrow or multiple spots in the body. So, for our purposes, we use them interchangeably, but that’s where the “multiple” comes from.

Katherine:

Okay. Isaac sent us this question. How long does the average myeloma patient remain on Revlimid? And, is there a suggested time period?

Dr. Richter:

Really great question. It depends upon the setting we’re looking at, and for the most part, a lot of people are probably asking about the maintenance setting. So, after initial therapy or after transplant, we put you on Revlimid. How long do we keep you on? The American adage has always been, “More is better,” so as long as you tolerate it and as long as it works. Outside of the U.S., they’ve done a couple of studies looking at one year and then stopping, or two years and then stopping.

And in a big trial that got presented a year or so ago, they compared the two years then stopping versus just staying on, and the people who just stay on do better.

So, now the current thinking is just keep you on long-term. What’s going to change that in the long term is we’re starting to use a technology called MRD, minimal residual disease, so, doing a marrow and trying to find one in a million or one in 10 million cancer cells.

And then, there’s something called sustained MRD meaning if you do two MRD analyses at least 12 months apart and they’re both negative, we call that sustained MRD negative.

And, there’s a hint that some people on maintenance Revlimid who have sustained their MRD negativity, they may do just as well stopping versus staying on it. We don’t know exactly who that is yet, but that’s going to be better understood in the next few years.

Katherine:

Okay. Randall writes, “I was diagnosed last year with myeloma, and my first treatment worked, but now I’ve relapsed. Is it too late to consider a second opinion or a consult with a specialist? Would that change anything?

Dr. Richter:

It’s a phenomenal question. There have actually been studies to show that if you engage with a myeloma center at least once within your myeloma journey, you do better than someone who has never done that. So, it is never a bad time to seek out a specialist. And one of the good things that came out of COVID is telemedicine. So, if there’s not someone right in your area, reaching out to some of our advocacy groups to help connect you to physicians like me or any of my colleagues, we’re more than happy to see anyone, I’ll see you with an MGUS that’ll never bother you, as will all of my colleagues and people who work in myeloma.

If you’ve had one prior line, 15 prior lines, anywhere in between. So, I think it’s always a good idea to see a specialist because he or she is more than happy to work with your local doctor to optimize your treatment without having to necessarily go to another center.

Katherine:

Yeah. Well, thank you for all of that, Dr. Richter. And, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. So, Dr. Richter, we’ve talked a lot about why patients should play a role in their care.

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their care?

Dr. Richter: So, that’s not always easy for a lot of people to do, and for some people, no problem. They’ll speak up at the first sign of anything. One bit of advice I would give to people who may have concerns or may not feel as comfortable about doing this is first of all, there’s a lot of members of the care team. So, I have patients that may not want to mention it to me, but mention it to my nurse or the medical assistant, and we all talk. So, that’s one way.

The other thing that I think may help is involvement in patient support groups, hearing what others have to say about similar experiences and learning from them, them learning from you, and that may actually give you more of a confidence to speak with your care team. But, the advocacy groups like the MMRF and IMF have tons of local support groups where you can sit in, and specialists come and speak or people share stories. And I think that can be really helpful to figuring out your optimal journey.

Katherine:

And knowing that you’re not alone –

Dr. Richter:

Absolutely.

Katherine:

– in how you’re feeling. As we close out this conversation, I wanted to get your take on the future of myeloma. What makes you hopeful?

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.

We are at the precipice of a brand-new Gestalt switch in myeloma.

The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”

And with so many great partners between advocacy groups and Pharma and patients and cancer centers, we’re going to collaborate and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.

Katherine:

Oh, I bet. I bet. It seems like there’s been so much progress and hope in the field. Dr. Richter, thank you so much for joining us today. It’s been a pleasure.

Dr. Richter:

Thank you so much for having me. I’d love to come back anytime.

Katherine:

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 for joining us.

How Can Clinical Trials Be Accessed?

How Can Clinical Trials Be Accessed?  from Patient Empowerment Network on Vimeo.

Clinical researcher Dr. Seth Pollack and patient advocate Sujata Dutta explain the benefits of participating in a clinical trial. They review important questions to ask your doctor and share advice for finding a trial.

Dr. Seth Pollack is Medical Director of the Sarcoma Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and is the Steven T. Rosen, MD, Professor of Cancer Biology and associate professor of Medicine in the Division of Hematology and Oncology at the Feinberg School of Medicine. Learn more about Dr. Pollack, here.

Sujuta Dutta is a myeloma survivor and empowered patient advocate, and serves a Patient Empowerment Network (PEN) board member. Learn more about Sujuta, here.

See More from Clinical Trials 101

Related Resources:

What Is a Clinical Trial and What Are the Phases? 

Are Clinical Trials Safe?

A Patient Shares Her Clinical Trial Experience


Transcript:

Katherine Banwell:    

Sujata, there’s clearly a lot of hesitation and misconceptions out there. What would you say to someone who’s considering a trial but is hesitant?

Sujata Dutta:  

I would say speak to your provider, speak to your doctor, and get all these myths kind of busted to say, “it’s going to be expensive” or whatever those questions are. And then, through that process also try and understand what is it that the study is trying to achieve? How is that going to be beneficial to you? So, in my instance, it wasn’t the last line of defense, it was just one of the processes or combos that would help me. And so, that was important for me to understand and then a little bit of education as well. So, I was asking, I have questions on my phone every time I meet my provider, and I did the same thing. So, I think that one of the good practices is keep your note of your questions and have those questions ready. And no question is silly, all questions are important. So, ask as many questions as you can and use that opportunity to educate yourself about it.

And maybe you realize, “No. I don’t think it’s working for me” or “I don’t think this trial is good for me.” But it’s good, important, to have that conversation with your provider, that’s what I would recommend highly.

Katherine Banwell:    

Excellent. Thank you, Dr. Pollack, if someone is interested in participating, how can they find out about what trials are even available for them?

Dr. Seth Pollack:       

Yeah. I mean, the best thing to do is to start just by asking your doctor if they know about any clinical trials. And a lot of the times the clinical trials are run at the big medical centers that may be closer to you, so you could ask your doctor if there’s any clinical trials at the big medical center even. Or I always think it’s good to get a second opinion, you could go get a second opinion at the big medical center that’s close to you and ask them what clinical trials are at your center.

And sometimes they’ll be conscious about some of the clinical trials that may be even run around the country. And you can ask about that as well.

Katherine Banwell:    

Would specialists have more information about clinical trials than say a general practitioner?

Dr. Seth Pollack:       

So, I specialize in rare cancers, so a lot of the times the general practitioners they’ve got my cell phone number, and they text me, and they say, “Hey, do you have a clinical trial going on right now?” And that happens all the time, but yeah, the specialists will usually because frankly there’s so much to know. And the general practitioners really have a lot to keep track of with all the different types of diseases that are out there. Whereas at the big centers, the specialists, part of their job is really to keep their tabs on what’s going on with the clinical trials.

So, they’re good people to ask, either your local doctor could reach out to them, or you could go get a second opinion and ask.

Sujata Dutta:  

There’s also a lot of information, Katherine, on sites such as LLS, or PEN, or American Cancer Society that they also publish a lot of information. Of course, I would recommend once you have that information then vet it by your specialist, or whatever. But if you’re interested in knowing more about clinical trials in general and some that would work for you, then those are also some places to get information from.

Katherine Banwell:    

That’s great information. Thank you, I was going to ask you about that Sujata. Well, before we end the program, Dr. Pollack, I’d like to get your final thoughts. What message do you want to leave the audience with related to clinical trial participation?

Dr. Seth Pollack:       

Yeah. I think clinical trials it can be a very rewarding thing for a lot of patients to do, I think patients really like learning about the new treatments. And I think a lot of patients really like being a part of pushing the therapies forward in addition to feeling like sometimes they’re getting a little bit of an extra layer of scrutiny, because there’s a whole extra team of research coordinators that are going through everything.

And getting access to something that isn’t available yet to the general population. So, I think there’s a whole host of advantages of going on clinical trials, but you need to figure out whether or not a clinical trial is right for you.

Katherine Banwell:    

Yeah. Sujata, what would you like to add?

Sujata Dutta:  

Absolutely, I second everything that Dr. Pollack is saying. And in my personal experience I wouldn’t say everything is hunky-dory, everything is fine. I’m going through treatment, I have chemo every four weeks, I started with chemo every week. That’s when the logistics pace was really difficult because going to Mayo every week was not easy. But anyways, as the trial progress itself every four weeks, but as I said the benefits are huge because I have labs every four weeks. I meet my provider every four weeks.

So, we go through the labs and anything amiss, I’ve had some changes to my dosage because I’ve had some changes in the labs. And so, there’s a lot of scrutiny which I like, but the flip side, for maybe some maybe like, “I have to have chemo every four weeks. Do I want to do that or not?” Or whatever. In my case, I knew it, and I signed up for it, and I’m committed to doing that for two years. And so, I’m fine with that. So, I would say all in all, I’d see more benefits of being in a clinical trial. One, you’re motivated to give back to the community. Two, you are being monitored and so your health is important to your provider just as it is to you. And so, I highly recommend being part of a trial if it works for you and if you’re eligible for one.