Tag Archive for: Monoclonal Antibody

CAR T-Cell Therapy | Transforming Myeloma Patient Care

Dr. Rahul Banerjee, a myeloma specialist and researcher, describes how CAR T-cell therapy has revolutionized care for people with myeloma. Dr. Banerjee discusses recent advances in research, citing specific studies that are having an impact, and goes on to review the currently FDA-approved CAR T-cell therapies.

Dr. Rahul Banerjee is a physician and researcher specializing in multiple myeloma and an assistant professor in the Clinical Research Division at the University of Washington Fred Hutchinson Cancer Center in Seattle, WA. Learn more about Dr. Rahul Banerjee.

Related Resources:

Myeloma CAR T-Cell Therapy | How Is Success Measured?

Myeloma CAR T-Cell Therapy | How Is Success Measured?

Myeloma Research | Updates in CAR T-Cell Therapy

Myeloma Research | Updates in CAR T-Cell Therapy

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment? 

Transcript:

Katherine Banwell:

We’ve been talking about CAR T-cell therapy for a number of years now. How has this treatment revolutionized care for patients? 

Dr. Rahul Banerjee:

Absolutely. So, the biggest benefit of CAR T therapy, I think, is how well it works. So, I’ll predominantly focus on multiple myeloma, but of course there are CAR T therapies that are approved for different kinds of lymphoma, and B-cell leukemia as well. But in brief, CAR T therapy, we train the immune system to fight back against the myeloma, against the cancer that’s there. And it’s phenomenal, because it’s the only living drug we have, really, in our toolbox. Everything else is dependent on the dose, right? As soon as the drug is out of your system, it stops working. CAR T cells don’t work that way. They can live and expand and proliferate to get rid of the threat within. 

And at least in myeloma, for example, CAR T therapies regularly have response rates, meaning complete response rates, how quickly they knock all the myeloma parameters down to zero basically in the 70, 80, 90 percent range. Many patients achieve measurable residual disease, or MRD negativity, meaning by all the best tools available in 2024, no sign of the myeloma anywhere.  

That doesn’t mean cure, to be fair, but that’s wonderful. With other conventional therapies, to have one drug with one infusion have that big of an impact on the myeloma is phenomenal.  

The other benefit of CAR T therapy is that it is a one-time infusion. It doesn’t mean that patients can get one-time CAR T and never have to see a cancer doctor again because again, at least in myeloma, I don’t consider CAR T to be uniformly curative for patients. However, if you look at the studies, and there’ve been two randomized studies in myeloma of CAR T therapy versus standard therapies. One was a KarMMa-3 trial with a drug called ide-cel, a CAR T drug also known as Abecma. And the other one was CARTITUDE-4, which was a study of cilta-cel versus standard treatment. And cilta-cel is a kind of CAR T also known as Carvykti.  

Both studies saw improvements, dramatic improvements in the response rate, how many patients had the myeloma numbers come down, but also durations of response and progression-free survival. How long patients were alive and disease-free for.  

Literally just a month ago, we found out officially that the cilta-cel trial and the CARTITUDE-4 study, CAR T actually prolonged overall survival compared to standard therapies, which is what patients are looking for.  

But for me, what I love about CAR T the most is not just that you’re in remission for longer, or with cilta-cel you live longer, but that you live better. Both studies, and I’m very happy to see this incorporated, what we call patient-reported outcomes, which is an area of research of mine. Patient-reported outcomes are, as you can imagine, outcomes that are reported by the patient. Not the blood test for the myeloma, but how are patients feeling in terms of their quality of life, in terms of their fatigue, in terms of their pain.  

And in both studies, off the charts. CAR T does way better and way faster in terms of improving quality of life than standard treatments, to the point where the studies, for example, often for both of them, if I recall correctly, the first time point where they looked and compared the two arms was three months after CAR T. And already by then, night and day difference.  

The patients who got CAR T, the first month a little bit rocky, but after the first month or two, they’re doing better, because they’re not on myeloma treatments continuously. They’re still getting blood work checked and so forth, but they’re not on treatment. It’s a one-time infusion and monitoring thereafter.  

And I love that about it, and I think that explains a lot of the quality of life benefits that we see.  

For my other patients with myeloma, outside of CAR T, there is never a scenario where they’re observed. The vast majority of patients because myeloma is considered incurable, we keep them on some form of maintenance treatment, and those come with side effects. Those come with financial toxicity. That’s the word we use for high out-of-pocket costs. They come with what I would call time toxicity. That’s time spent on the phone coordinating shipments or coming in for this infusion or that infusion. 

CAR T has much less of that, and I think that’s phenomenal. So, I would say that it’s revolutionized the field, not just scientifically from the things that you’d expect a researcher to care the most about – for how long, you know, how deep are their remissions and how durable are their remissions, but also for the things that I care about. The art of oncology is how our patients are living, and that’s why I think CAR T is revolutionary. 

Katherine Banwell:

Dr. Banerjee, would you walk us through the currently approved CAR T-cell therapies for myeloma and share how these treatments work to combat myeloma? 

Dr. Rahul Banerjee:

Absolutely so. So, there’s two FDA-approved CAR T therapies right now for multiple myeloma. One is ide-cel, also known as Abecma. One is cilta-cel, also known as Carvykti. The mechanics of them are pretty similar. Both involve T cells being collected from the patient and then turned into CAR T cells, cancer fighting cells in a lab, then put back into the patient after a small dose, what we call lympho-depleting chemotherapy, that creates a void and makes room for the T cells. 

And then the T cells come in and are able to activate and proliferate and respond and kill off the myeloma. In terms of the two drugs, the differences between them, we might come back to that a bit in terms of just how they’re approved. Cilta-cel is currently approved as early as first relapse. So, second line treatment onwards in myeloma for patients who have disease that is refractory to lenalidomide (Revlimid) or a similar class of drugs.  

So, lenalidomide is Revlimid. So, if someone’s been on Revlimid and it stopped working, they could technically go to cilta-cel, which is Carvykti, as soon as second line. 

Ide-cel or Abecma is approved for third line treatment, meaning at least two prior relapses or two types of therapy that were stopped unexpectedly because of not working or toxicities or so forth. And those patients would have had to have received both an iMiD, like Revlimid, which is lenalidomide, a proteasome inhibitor, which is like Velcade or bortezomib, and a CD38 directed monoclonal antibody like daratumumab, which is also called Darzalex or Darzalex Faspro. 

Evolve | What You Should Know About Advances in CAR T-Cell Therapy for Myeloma

How is CAR T-cell therapy revolutionizing care for people with myeloma? Dr. Rahul Banerjee, a myeloma expert and researcher, shares an overview of how CAR T-cell therapy is evolving, important factors to consider when choosing to undergo this treatment, and how advances in research are impacting myeloma care. 

Dr. Rahul Banerjee is a physician and researcher specializing in multiple myeloma and an assistant professor in the Clinical Research Division at the University of Washington Fred Hutchinson Cancer Center in Seattle, WA. Learn more about Dr. Banerjee.

Download Resource Guide

Related Resources:

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care? 

Transcript:

Katherine Banwell:

Hello and welcome. I’m your host, Katherine Banwell. Today’s program is part of the Patient Empowerment Network’s Evolve series, which was developed to provide you with the latest treatment information and research, helping you to feel empowered and confident during conversations about your care. In today’s program, we’re going to hear from an expert in the field discussing CAR T-cell therapy and the evolving treatment landscape. 

Before before we get into the discussion, please remember that this program is not a substitute for medical advice. Please refer to your healthcare team about what might be best for you. Joining us today is Dr. Rahul Banerjee. Dr. Banerjee, it’s so good to see you. Welcome. Would you please introduce yourself? 

Dr. Rahul Banerjee:

Of course. Thank you, Katherine, for taking the time to interview me. Thank you to everyone who’s listening. My name is Dr. Rahul Banerjee. I’m an Assistant Professor of Medicine at the Fred Hutchinson Cancer Center in Seattle, Washington.  

I specialize in multiple myeloma, which is a form of blood cancer that we’ll talk about, and other precursor conditions, for example, smoldering myeloma and AL amyloidosis. I have a heavy interest in CAR T therapy and bispecific antibodies and other types of immunotherapy for blood cancers, and I’m sure we’ll be speaking about that as well. It’s great to be here. 

Katherine Banwell:

And thank you so much for taking time out of your busy day. I’d like to start by talking about your role as a researcher. You’re on the front lines for advancements in the myeloma field. What led you here, and why is it important to you? 

Dr. Rahul Banerjee:

Absolutely. So, the short answer is that I love the art and the science of oncology, of cancer care. I feel like it really gives us a great chance to work with patients and really help them through the difficult chapter of their life. And the science, particularly in malignant hematology, is a word we use for blood cancers like myeloma, lymphoma, et cetera. There’s a lot of fascinating science about how do we train the immune system to overcome cancers of immune cells? 

In terms of why myeloma, you’ll probably hear this from many physicians who speak on this program. Part of it is the patients, and I love treating my patients with myeloma. They have the most interesting stories for me. Many of them are older and have been through a lot, and I worked with them for years for diagnosing myeloma, treating them through myeloma, monitoring for relapses, and so forth. 

And also the mentors whom I had. So, when I was a trainee in fellowship, I was not sure where I would go. I knew it was somewhere within blood cancers, but I had a mentor, Dr. Nina Shah, who is phenomenal, and she did a lot of work in multiple myeloma in particular, including around CAR T therapy, and I kind of molded myself, imprinted myself on her. And now several years later, here I am kind of working in this similar space, focusing again at the intersection of multiple myeloma and these immunotherapies, like CAR T therapy. 

Katherine Banwell:

We’ve been talking about CAR T-cell therapy for a number of years now. How has this treatment revolutionized care for patients? 

Dr. Rahul Banerjee:

Absolutely. So, the biggest benefit of CAR T therapy, I think, is how well it works. So, I’ll predominantly focus on multiple myeloma, but of course there are CAR T therapies that are approved for different kinds of lymphoma, and B-cell leukemia as well. But in brief, CAR T therapy, we train the immune system to fight back against the myeloma, against the cancer that’s there. And it’s phenomenal, because it’s the only living drug we have, really, in our toolbox. Everything else is dependent on the dose, right? As soon as the drug is out of your system, it stops working. CAR T-cells don’t work that way. They can live and expand and proliferate to get rid of the threat within. 

And at least in myeloma, for example, CAR T therapies regularly have response rates, meaning complete response rates, how quickly they knock all the myeloma parameters down to zero basically in the 70, 80, 90 percent range. Many patients achieve measurable residual disease, or MRD negativity, meaning by all the best tools available in 2024, no sign of the myeloma anywhere.  

That doesn’t mean cure, to be fair, but that’s wonderful. With other conventional therapies, to have one drug with one infusion have that big of an impact on the myeloma is phenomenal.  

The other benefit of CAR T therapy is that it is a one-time infusion. It doesn’t mean that patients can get one-time CAR T and never have to see a cancer doctor again because again, at least in myeloma, I don’t consider CAR T to be uniformly curative for patients. However, if you look at the studies, and there’ve been two randomized studies in myeloma of CAR T therapy versus standard therapies. One was a KarMMa-3 trial with a drug called ide-cel, a CAR T drug also known as Abecma. And the other one was CARTITUDE-4, which was a study of cilta-cel versus standard treatment. And cilta-cel is a kind of CAR T also known as Carvykti.  

Both studies saw improvements, dramatic improvements in the response rate, how many patients had the myeloma numbers come down, but also durations of response and progression-free survival. How long patients were alive and disease-free for.  

Literally just a month ago, we found out officially that the cilta-cel trial and the CARTITUDE-4 study, CAR T actually prolonged overall survival compared to standard therapies, which is what patients are looking for.  

But for me, what I love about CAR T the most is not just that you’re in remission for longer, or with cilta-cel you live longer, but that you live better. Both studies, and I’m very happy to see this incorporated, what we call patient-reported outcomes, which is an area of research of mine. Patient-reported outcomes are, as you can imagine, outcomes that are reported by the patient. Not the blood test for the myeloma, but how are patients feeling in terms of their quality of life, in terms of their fatigue, in terms of their pain.  

And in both studies, off the charts. CAR T does way better and way faster in terms of improving quality of life than standard treatments, to the point where the studies, for example, often for both of them, if I recall correctly, the first time point where they looked and compared the two arms was three months after CAR T. And already by then, night and day difference.  

The patients who got CAR T, the first month a little bit rocky, but after the first month or two, they’re doing better, because they’re not on myeloma treatments continuously. They’re still getting blood work checked and so forth, but they’re not on treatment. It’s a one-time infusion and monitoring thereafter. 

And I love that about it, and I think that explains a lot of the quality of life benefits that we see.  

For my other patients with myeloma, outside of CAR T, there is never a scenario where they’re observed. The vast majority of patients because myeloma is considered incurable, we keep them on some form of maintenance treatment, and those come with side effects. Those come with financial toxicity. That’s the word we use for high out-of-pocket costs. They come with what I would call time toxicity. That’s time spent on the phone coordinating shipments or coming in for this infusion or that infusion. 

CAR T has much less of that, and I think that’s phenomenal. So, I would say that it’s revolutionized the field, not just scientifically from the things that you’d expect a researcher to care the most about – for how long, you know, how deep are their remissions and how durable are their remissions, but also for the things that I care about. The art of oncology is how our patients are living, and that’s why I think CAR T is revolutionary. 

Katherine Banwell:

Dr. Banerjee, would you walk us through the currently approved CAR T-cell therapies for myeloma and share how these treatments work to combat myeloma? 

Dr. Rahul Banerjee:

Absolutely so. So, there’s two FDA-approved CAR T therapies right now for multiple myeloma. One is ide-cel, also known as Abecma. One is cilta-cel, also known as Carvykti. The mechanics of them are pretty similar. Both involve T-cells being collected from the patient and then turned into CAR T-cells, cancer fighting cells in a lab, then put back into the patient after a small dose, what we call lympho-depleting chemotherapy, that creates a void and makes room for the T cells. 

And then the T cells come in and are able to activate and proliferate and respond and kill off the myeloma. In terms of the two drugs, the differences between them, we might come back to that a bit in terms of just how they’re approved. Cilta-cel is currently approved as early as first relapse. So, second line treatment onwards in myeloma for patients who have disease that is refractory to lenalidomide (Revlimid) or a similar class of drugs.  

So, lenalidomide is Revlimid. So, if someone’s been on Revlimid and it stopped working, they could technically go to cilta-cel, which is Carvykti, as soon as second line. 

Ide-cel or Abecma is approved for third line treatment, meaning at least two prior relapses or two types of therapy that were stopped unexpectedly because of not working or toxicities or so forth. And those patients would have had to have received both an iMiD, like Revlimid, which is lenalidomide, a proteasome inhibitor, which is like Velcade or bortezomib, and a CD38 directed monoclonal antibody like daratumumab, which is also called Darzalex or Darzalex Faspro.   

Katherine Banwell:

CAR T therapies have been in use for several years now. As a clinician, what challenges are you facing with this treatment option? 

Dr. Rahul Banerjee:

Absolutely. So, I would say threefold, is the best way to describe it. So, I think the first and most practical, like the most important one is obviously access. It’s very easy for me to talk about CAR T therapy. I had the privilege of working at a big center, where I was just last week attending on our CAR T service. We’re big enough to have a CAR T service. 

Most patients are treated in the community, and they don’t have access to a doctor who’s personally familiar with CAR T. And so for them to get to CAR T requires a move to a big academic center, a big tertiary care center. Obviously, I think this talk is geared more towards the U.S. audience, but most of the world has no access to CAR T, period, except for research protocols, and that makes things really tough. So, I think that’s one unmet need in general, where those patients who cannot get to CAR T never see me, and that’s a big disparity in the field.  

Two, I would say that the autologous CAR T products we have, autologous is the word that we use for the T cells that are coming from the patient themselves. Both Abecma and Carvykti, again, it’s the patient’s own cells that are being taken out, turned into CAR  
T cells, and put back. That manufacturing process takes time. Typically, I tell patients to expect about one to two months, closer to two months often, between the day that the T cells are taken out and the day they’re put back in again, what we often call the quote unquote “vein-to-vein interval.” And that’s hard because for some patients that’s not practical. 

The myeloma is, you know, so aggressive, behaving aggressively, that they cannot wait. There’s no drug I can give them where I can wait two months for the T cells to be manufactured. We’re getting better at it. The drug company is working better at it. There are a lot of investigational products that are not FDA approved yet that are looking at rapid manufacturing, where can you grow these  
T cells and the CAR T cells in two days or one day, instead of several weeks? I think that’s really interesting. 

There are studies of allogeneic CAR T cells, where the T cells are pre-manufactured from a healthy donor and manipulated so they won’t cause any other problems, but will attack the myeloma. So, a lot of research happening there, but that’s the problem for patients where they cannot get to CAR T therapy.  

And then the third unmet need would be – I’m seeing more of this, unfortunately, right? CAR T therapy is not considered curative for myeloma. Have I met people who are doing great years out from myeloma? Yes, from CAR T therapy, and I love that. In the original LEGEND-2 study, the study that led to the CARTITUDE-1 study that led to the approval of cilta-cel, which is Carvykti. 

If I recall correctly, about 20 percent of patients on that first Chinese study years ago are alive and disease-free five years later. That’s not enough, right? I don’t want it to be 20 percent, I want it to be 100 percent. And so we have work to be done there in terms of what do we do when the myeloma, the CAR T cells stop working, or they’re out of the system and are no longer there to fight back. What do we do next? And I think that’s another unmet need still. Despite all the advances, what to do after CAR T, no one really knows. 

Katherine Banwell:

Yes. Well, how is success measured for CAR T-cell therapy? 

Dr. Rahul Banerjee:

It’s a great question. So, traditionally, the metric in multiple myeloma has been achieving a complete response. So, having the M-spike, the antibodies that are produced by the myeloma cells, come down to zero.  

So, either the M-spike, or for some patients, that may be the kappa or the lambda, which are fragments called light chains of antibodies, coming down to the normal range. The hard thing about those is that they take time. I’ve had patients who get CAR T therapy, and their bone marrow is completely clear, including MRD, measurable residual disease, as I’ll talk about in a second, but the M-spike takes months. 

I had one patient where it took a year and a half for the M-spike to finally come down to zero. And it’s frustrating because I would say that, look, in my heart, you’re in remission, but if I were a lawyer, I wouldn’t be able to say that, because technically the M-spike is not quite zero yet. Your body’s just recycling that antibody. It’s not all the way down to zero, and that makes things tough. So, I don’t think that’s a great barometer to use.  

I think MRD, which is again, a bone marrow test that we can spend more time talking about another day, is helpful. And at the one-month mark, achieving MRD negativity.  

So, if you look in the bone marrow, by all the best tests available in the United States in the year 2024, and you can’t even find one out of a million cells that are myeloma, that’s obviously great to see.  

That doesn’t mean that if it doesn’t happen, the patients are going to do poorly. There’s a lot more to CAR T than that. So, I think MRD negativity is probably the best short-term barometer. I think the best long-term barometer would be progression-free survival, which is, again, the medical word of saying how long is someone alive and in remission for. 

With cilta-cel, which is Carvykti, again, in the CARTITUDE-1 study, which led to its approval, its first approval for four prior lines of therapy. There, most patients, the median progression-free survival was 35 months. So, almost three years. That’s amazing, right? Three years of mileage of coming in for blood work, some supportive care, IVIG, which is a type of antibody transfusion, but not needing myeloma treatment. That’s great. That’s the bar that we’d be looking for from an efficacy perspective. I think the other thing, just to talk about it, I’m sure we’ll come back to it, would be safety, right? Because these cells, these therapies do come with side effects.  

And so I think the other bar by which, in the future, I may compare CAR T therapies as more come to market, would not just be this progression-free survival, which is how long are patients in remission for and disease-free and alive. Not just MRD negativity, which is how the bone marrow biopsy looks at day 28, one month after CAR T. But also the safety profile. Are we seeing any scary, concerning, delayed toxicities? And if we don’t, that would be another bar for success in my mind, especially as we move CAR T to earlier lines, where other treatments are available. 

We have to make sure that the benefit-risk ratio for CAR T remains favorable. 

Katherine Banwell:

Yes. Well, let’s talk about side effects of CAR T-cell therapy. What advances are being made in managing them? 

Dr. Rahul Banerjee:

Excellent question. So, I break the toxicities into short-term and long-term toxicity of CAR T therapy. And this is actually fairly similar for both, regardless of the underlying disease, whereas lymphoma, leukemia, or myeloma, very similar. Just so everyone, just to reorient the audience, short-term toxicities, people often talk about the big two. I’m going to say the big three, actually. The first one is cytokine release syndrome, or CRS, which is inflammation, typically causing fever, sometimes low blood pressure. 

The second is neurotoxicity, or ICANS. For reasons that aren’t entirely understood, sometimes all those chemicals from inflammation can cause people to feel a bit off mentally or cognitively. Sometimes people might not be able to talk, or might not talk correctly, or sometimes have issues along those lines. 

And the third, I would say, is low blood counts or infections. Both the lymphoma, leukemia CAR Ts and the myeloma CAR Ts very rapidly deplete the good plasma cells or the good lymphocytes, the good cells in the bone marrow, and so immediately you see patients at risk of infections. 

And for a complicated number of reasons, one of which being cytokine release syndrome, CRS inflammation within the bone marrow, where all these cancer cells are hiding, the stem cells in the bone marrow hide away, right? They kind of go into a bunker to stay away from all of this. And so patients often have low blood counts for significant amounts of time after CAR T therapy, something called hematotoxicity. 

Those are short-term toxicities. Long-term, very briefly, that risk of infection and low blood counts is still there, I would say, for up to a year after CAR T therapy, sometimes longer for some patients. There is a risk, obviously, of the original cancer coming back, in this case the myeloma, particularly myeloma.  

And three, there are rare delayed toxicities to be on the lookout for. So, one of them, for example, with cilta-cel or Carvykti, the numbers are hard to see what the rate is prospectively because it’s been going down with time.  

But rarely, I would truly in my heart say 1 percent of the time, if not less, patients can get Parkinsonism, where they’re not able to move as rapidly, they’re not able to, they’re kind of shuffling gait, having tremors, et cetera. Not the same as normal Parkinson’s disease, because the normal meds don’t work, just time is often the only thing that really makes a big difference. 

Technically, there’s a box warning on all CAR T therapies now about a risk of second cancers. That risk is not new to anyone who’s ever received any treatment for myeloma because from the very beginning, we tell people that these drugs have been linked to a potential risk of second cancers in the future.  

In terms of strides that are being made to improve that, I think we’re making a lot of improvement. So, I think the biggest thing that we’ve learned, and I remember when I was a trainee, for example, when I was in my medical training, the early days of CAR T therapy – actually out in Philadelphia, I trained at Penn – and there, we were scared about trying to tone down the inflammation.  

When these side effects happen in the short term, the goal is if the patient’s obviously having side effects, and the question is, “Can we not kill the T cells? Can we just dial that down?” Say, “Look, I’m happy the T cells are angry. I’m happy they’re killing the cancer, the myeloma in this case. But can you just dial it down a little bit with a medication called tocilizumab (Actemra), or corticosteroids like dex?” 

We used to be very nervous about doing that because we said, look, the patient’s put all this blood, soil, sweat, and tears right into this CAR T therapy, and we don’t want to do anything that can hinder the T cells from working.  

Now we know that that level of inflammation is not doing anyone any favors at all, and so we’re able to really start these medications to just dial down the immune system faster. As soon as someone has a fever, for example, at many centers, we do consider, within an hour or two, giving one of those medications. Don’t wait till they’re in the ICU, give it then.  So, I think just tweaking our algorithms has made probably the biggest difference, in my mind, to make CAR T safer.  

Other things that have helped, I think, are better understanding of why patients have these other toxicities and strategies to prevent it. And so, for example, the neurotoxicity risk, some of it is part of disease burden. We think that patients who have a lot of disease going into CAR T therapy may have more toxicities. So, giving better treatments as, quote-unquote, “bridging treatment” before CAR T therapy that we have better, newer treatments now, have sometimes helped to really debulk the disease before going to  
CAR T.  

That’s helped a lot with side effect management. In terms of long-term risk, the third thing that I really encourage all my patients and all my oncologist partners in the community to really push for is the infection risk and how do we prevent it? So, I think probably the biggest thing that we’ve recognized is intravenous immunoglobulin, which is IVIg, which is basically an antibody transfusion.  

When people donate blood, they also donate plasma, often, and the plasma contains antibodies against whatever they themselves have fought off circulating in the area – viruses, colds, et cetera. 

You can take all those antibodies, put them all together into a sterile bag, and give it to the patient who’s gotten CAR T therapy. Because the patient’s gotten CAR T therapy, assuming it’s working, which it normally does for several months, right, to knock out all cells, good and bad immune cells, that patient is not making any antibodies at all. They’re a sitting duck for infections. And so I would say IVIg, using that routinely now is not just the exception once they’re having infections, but even in the absence of infections, just giving it.  

Insurance companies are not happy with me when I suggest that because it’s expensive, but that’s the right thing to do for patients, and I think that has helped a lot, in my experience, for all of these immunotherapies, both CAR T and bispecific antibodies, to lower the risk of infections.  

Katherine Banwell:

Can you share any updates in CAR T-cell therapy research? 

Dr. Rahul Banerjee:

Sure. So, several. I would say the first, I alluded to very briefly earlier, was how do we make that vein-to-vein time shorter? So, the vein-to-vein is, again, from the moment that the T cells are collected to when they’re put back into the patient.  

And so a lot of research is how do we make that better? We have rapid manufacturing protocols that, again, where the T cells are taken out and manufactured within a couple of days and brought back into the patient. They’re still testing for safety and sterility and everything that needs to be done, so it’s not overnight, but still, one or two weeks’ worth of vein-to-vein time is way better than one to two months.  

The allogeneic CAR T cells that are coming from a healthy donor, those are fascinating, right? Because if the cells are pre-manufactured, there’s no risk of them not manufacturing or manufacturing in an odd manner, what we call auto-specification. They’re ready from a healthy donor, ready to go. 

And one of the studies that was presented last month at our International Myeloma Society meeting in Brazil, the time, the median time from when the patient went on the study to when they started that lympho-depleting pre-CAR T therapy was one day, and that means they got CAR T therapy within one week of going on the study. That’s phenomenal. And so I think that research is ongoing.  

There are some side effects about allogeneic, healthy donor CAR  T-cells in terms of making sure the T cells stick around and don’t cause other issues. Sorry, for another day. I think that’s one area of research.  

I think the other big area of research is how do we make CAR T-cells work for longer for more people? There are easy ways, and there are controversial ways to do that. So, I think the easy way is can we use MRD negativity or other tests to identify who is at very low risk of relapse and monitoring them appropriately.  

There are patients where, in the future, we may talk about doing some form of post-CAR T maintenance therapy. Again, the bar for that should be set pretty high, and it is set pretty high because as I mentioned earlier, many patients prefer CAR T therapy, not just because of the deeper remissions and longer remissions, but because it truly is time away from treatment. But they’re still coming in for the IVIg and the blood work and seeing a doctor, et cetera, but they’re not getting daily treatment with lenalidomide, which is Revlimid, or pomalidomide, or Pomalyst, or something like that. And that’s wonderful. 

However, there may be some patients where some form of strategy will use one of those medications or experimental medications. There’s a newer class of the lenalidomide, Revlimid, pomalidomide, Pomalyst called CELMoDs.  

They’re not approved yet, but drugs like iberdomide or mezigdomide that work better, and not just against the myeloma. They actually make T cells stronger, believe it or not. 

And so in the future, there may be scenarios where we recommend for certain patients that, hey, in your particular case, after CAR T therapy, to keep the myeloma away, I’d recommend using this form of maintenance, a pill or something like that, just low dose to, again, keep the myeloma at bay and keep the T cells, in this case, the CAR T cells strong. So, I think those are all areas of exciting research.  

And then the last thing I would say is, we have several novel CAR T therapies that are being studied that may work better and safer than the existing products. Some of them, which are in early phase studies, actually target two proteins at once. The idea, going back to one of the earlier topics I mentioned, is that if the CAR T cells see that protein BCMA, they immediately destroy the cell that’s holding that. But what if the cell learns to turn off BCMA? All of a sudden, it’s invisible to the CAR T cells, and you’re right back to starting square one again. 

And so the idea is that there are CAR T cells that are being developed that target two proteins at once, kind of what’s called origating, where if it sees this or this, it’s immediately able to attach and bind that cell.  

The idea being that it’s easy for a myeloma cell – not easy. It’s possible for a myeloma cell, just by dumb luck, bad luck for the patient, to mutate in a way that shuts off that one protein. For it to simultaneously be able to do that for two separate proteins at once, the odds are much lower.  

And so the idea with dual targeting is you may be able to knock out more cells more durably, or even knock out the myeloma precursor cells that aren’t quite myeloma cells, but are there, what we call stem cells under the hood that are still malignant? So, a lot of those areas, I think, are really fascinating. Obviously, we need a lot more research in those particular areas before they’re ready for prime time. 

Katherine Banwell:

Yes. What is GPRC5D? 

Dr. Rahul Banerjee:

Great. Yes, so it’s a mouthful, is the best way to describe it. It’s an interesting protein. It’s a protein that, I alluded to that, it’s a second target that’s being targeted by some CAR T cells, for example, either in addition to BCMA or by itself. Several companies are looking at that in trials.  

GPRC5D is interesting because we don’t know what it’s for. BCMA, we know exactly what it’s for and why good and bad plasma cells, again, the bad plasma cells being the myeloma, why they express it. No one knows for GPRC5D.  

In the field, we’ve put almost all of our myeloma eggs into the BCMA basket, historically speaking, and all the approved immunotherapies, CAR T and bispecifics in myeloma, with one exception, which is talquetamab or TALVEY, all target BCMA. So, we need to not put all our eggs in that basket. And so GPRC5D targeted therapies, again, there was one approved bispecific antibody, which was not the focus of today’s talk, called talquetamab or TALVEY.   

There are investigational CAR T products that target GPRC5D as well. At least from the limited experience that we have, there seems to be no correlation between them.  

In the future, do we know that someone needs to get BCMA therapy first and then GPRC5D therapy later? We don’t know that, actually, and that’s one of our areas of research and one of my areas of research as well. What if we do it the other way around, right? What if we give GPRC5D first and then do BCMA? We don’t know. 

So, I think one of the big questions in the field is sequencing, which is the word of like, what drug do we use first and when? We’re working on a paper, the International Myeloma Working Group is working on a big, extensive paper to try to put all the evidence together, but that’ll be a moving target.  

Katherine Banwell:

Yes. Patient participation is essential in advancing myeloma research. How do clinical trials impact care? 

Dr. Rahul Banerjee:

Absolutely. So, phenomenally and importantly, I think it’s a short answer. It’s worth noting that clinical trials come in all shapes and sizes. People often assume that clinical trial means, by default, a Phase I study, first time in human being, a quote-unquote “guinea pig.” That’s true for a minority of studies, and that’s very important for us to understand how best to make the drug work better. I would say the vast majority of trials that I put my patients on are not like that. They’re often bigger Phase II or Phase III studies. 

As an example, you know, both Abecma and Carvykti, those were already approved in later lines, but to get them approved in earlier lines, we had to run a study of using them earlier versus not using them earlier. So, that’s a good example where the drug is FDA-approved, it’s just the sequencing of it that’s new.  

There are trials of supportive care. We’ll be opening a study, I alluded to this, the side effects of GPRC5D targeted therapies with taquetamab. We’ll be opening a study that randomizes patients to one of four different supportive care strategies to figure out which one actually works to make the taste issues better. Because we don’t know until we try, right? If we don’t do a rigorous study, and we just go by, “Oh, I had one patient once where this worked, and one patient once where this worked,” that’s not a scientific way of answering questions, and we’re not really able to advance the field to help all patients.  

So, that’s where I think clinical trials come in handy. That, and I alluded to all these newer investigational CAR T therapies that might actually work better and be safer than the existing one. They’re all coming through investigational trials.  

So, trials is kind of how we get these drugs, one, these newer ones to market, but also how we learn to make them better. And we have trials, all sorts of trials, looking at all sorts of, again, not just new drugs, but also where to put the drugs, right? Where to sequence the CAR T therapies, or what supportive care strategies do we use? And the trials are kind of the linchpin of making the field work better. Again, not just for some patients who happen to do well, but for all patients. The only reason we’ve found out what works for all patients is by doing clinical trials.  

Katherine Banwell:

I’d like to get to a few questions that we received from our audience members prior to the program.  

Dr. Rahul Banerjee:

Yes, of course. 

Katherine Banwell:

This one is from Jennifer. Why do CAR T-cell transplants not last longer? Is it possible to do a second transplant if the first CAR T transplant stops working?  

Dr. Rahul Banerjee:

It’s a great question. So, it’s an excellent question. So, the only thing I would say semantically is, right, in my head, CAR T cells are not transplants per se, because I’m not changing the bone marrow. So, I would transplant a stem cell transplantation, separate from CAR T.   

Why do CAR T cells stop working? So, the short answer is we can speculate. We don’t know for sure for any individual patient. Three different buckets are involved. Three different things can happen. One, the T cells can stop working or disappear from circulation. So, that’s possible. CAR T cells don’t last forever. That’s actually okay, right? People often wonder like, “Man, I wish the CAR  
T cells could last forever.” I don’t know that I’d want that because as I alluded to, for as long as the CAR T cells are there, patients are immunocompromised, and so that can certainly interfere with the quality of life.  

So, it’s not necessarily true that the CAR T cells need to be there forever, but if they’re not there, or if they’re exhausted, which is actually a true scientific word for them not being able to activate and kill that cell when they recognized a protein, the BCMA, that’s one problem.  

The second problem is the myeloma cells can mutate. I alluded to this briefly earlier, where the cells can learn to shut off the protein, BCMA, or they can mutate the protein in just a way that the CAR T is no longer able to bind.  

And the third is something called the tumor microenvironment. And this is a little bit more complicated, kind of a grab bag of different things here. The idea is that myeloma cells have a lot of tricks, and they can use all of the cells around them to make it hard for the CAR T cells to get in, to get into the bone marrow and kill them all. And the T cells can be shut off before they even get there.  

So, it’s one of those three things in general. Which one is it for an individual patient? Hard to say. And so hopefully in the future, we’ll have better diagnostic tests to be able to identify who is a patient where another BCMA targeted therapy would work well versus, “Oh no, these myeloma cells are no longer expressing BCMA, let’s move on to a different target like GPRC5D.” We’re not there yet. We’ll get there hopefully in a couple of years, is my goal.  

Then, you know, Jennifer, that’s a good question. Well, can we do a second CAR T? And that’s very practical. What I would say is if the first CAR T therapy did what we expected it to do, if it lasted for as many years as I would expect for Abecma, that’s typically 12 to 18 months. For Carvykti, that’s typically over 24 months.  

If it worked and then it stopped working, and then probably the T-cells are long gone, it’s reasonable to try CAR T therapy again. In general, I would recommend, I strongly recommend a different CAR T-cell therapy, even if it’s targeting the same class, like BCMA, it’s going from Abecma to Carvykti or vice versa. 

The risk with giving the same CAR T-cell product again is that even though the T cells are a patient’s own T cells, the protein is slightly foreign. Abecma was derived from decades of mouse research. Carvykti was made from decades of llama research, believe it or not. Again, there’s no mouse or llama involved with the actual products nowadays, but in making the sequence years ago that came to them, they are foreign. There are foreign sequences on them, and so everyone’s host immune system eventually recognizes these cells as foreign.  

And so if you were to give the exact same product again, immediately the body would reject it the second time around, because it recognizes them and has learned to recognize it as foreign. But changing to a different CAR T cell is very reasonable. 

And again, for these newer GPRC5D targeted CAR T cells that, again, don’t target BCMA the way that Abecma, ide-cel or cilta-cel, Carvykti do, but target a different protein entirely, for those patients generally there’s no restriction on whether they’d received a prior CAR T cells. Ideally, it should be at least several months away, at least like a year or so, but if that’s happened and they stopped working, very reasonable. In fact, some of the trials actually require that patients going on to the study of a GPRC5D product have had a prior BCMA therapy of some sort before, and so they’re kind of built into the architecture of things. So, I think it’s very reasonable.  

Obviously, there are some unknown unknowns, right? What do you do if the T cells are being manipulated twice, so to speak. Patients ask me about that. I will say just to put that fear to rest, in general, by the time that someone’s had myeloma come back after the first CAR T cells, I alluded to this, the CAR T cells are long gone. So, there’s nothing left. But again, every case is different, and future research will help us kind of figure out how best to do this. 

Katherine Banwell:

Yes. We have one more question from Rita. She wants to know if there is an age limit on CAR T-cell therapy. 

Dr. Rahul Banerjee:

It’s a brilliant question. So, in brief, no. It’s a short answer. My oldest patient who got the CAR T is in their 80s and handled it across all my years at UCSF and here at Fred Hutch. More important than chronological age is physiologic age in terms of how robust they are, how robust they feel in terms of going through this. What I recommend, I’ve heard of centers that do CAR T therapy for patients in their 90s, for example. So, I think it’s not so much age, it’s how fit they are. 

Fit is easy for me to say. What does that actually mean? Typically it’s a combination of, you know, like cognitively, how are people doing? Because obviously if someone has baseline dementia, which is pretty uncommon, for example, maybe CAR T is not the best use of their time. The biggest thing that I think gets some of my older patients in trouble is frailty.  

So, just not being as fit as they were before in terms of muscle strength, being able to move around quickly, and so forth, or cardiovascular issues. Because it’s worth noting that with CAR T therapies that we have now, probably 60, 70 percent of patients will get CRS, cytokine release syndrome. So, that’s fevers and low blood pressure, that’s what I said earlier.  

But if you think about it, a fever of 104 degrees Fahrenheit, your heart rate’s going to be like 130, 140 beats per minute, beating very fast for several hours, sometimes longer than that. If you’re having low blood pressure, it’s your heart that has to push blood to overcome that low blood pressure. Can someone’s heart handle that level of stress? As people get older, that obviously gets harder.  

So, if someone is already just 75 and were being considered for CAR T therapy, certainly I think it’s very reasonable to talk about it. I would ask someone where I may have them meet with a cardiologist beforehand, possibly a geriatrician as well beforehand, just to see how can we optimize their health to make CAR T as safe as possible for them? So, it’s definitely possible. 

Katherine Banwell:

Well, thank you for that, Dr. Banerjee. And those were all great questions. If you have more as part of the audience, please continue to send them to question@powerfulpatients.org, and we’ll work to get them answered on future programs.  

Dr. Rahul Banerjee:

Absolutely. 

Katherine Banwell:

Well, Dr. Banerjee, we learned that the field of myeloma care and CAR T-cell therapy is advancing quickly. As we close out the program, what are you excited about? Why are you hopeful? 

Dr. Rahul Banerjee:

Absolutely. So, I think I’m excited because, especially for CAR T therapy in particular, at our center, for example, we used to only be able to do like one or two patients per month. It was a very steady, low stream, because there were a lot of issues with manufacturing, and it was during the COVID pandemic, and there were supply chain issues, et cetera. 

And there were studies, and I remember them, very dark studies in 2021, 2022 even, that patients were more likely to die on the  
CAR T waitlist than they were to actually get CAR T therapy. That’s terrible. And we’ve come a long way since there, where our capacity, every year we’re doing more and more patients to CAR T therapy per month, which is wonderful. 

And so what I would say is that makes me hopeful, right? Because CAR T therapy, I’m not saying that everyone is required to get CAR T therapy. I have plenty of patients who hear about it and are like, oh, no thanks. I’d rather stay with what I’m getting right now with my local oncologist. And that’s okay, but I want it to be an option for as many patients as possible, and I think we’re making strides there. 

And so I think what I would say, the kind of closing words here is, we only can get you CAR T therapy if we know about your case and if you know about us. And so what I would say, I’m sure to people listening to this, you’re very motivated. And so you know the importance of having a myeloma specialist in your field. 

What I would say is my patients who do the best are the ones who are co-managed. They have a doc out in the community. I have patients from Idaho, Montana, Alaska, Eastern Washington, et cetera. They have an oncologist who knows them well, who knows their community well, easy to get to, can handle everything. They’re a jack of all trades and very good at it. And then they have me, who they see periodically for CAR T evaluation, just discussions about CAR T by telehealth, something along those lines. 

And I’m able to talk about CAR T therapy in detail and answer their questions. And so what I would say is, I’m hopeful that that trend will continue, and that if someone’s even interested in hearing about CAR T therapy, they don’t meet me for the first time when they actually need CAR T therapy right then and there. They meet me years beforehand to just talk about CAR T, so they know it’s an option for them. 

And that time – because we don’t have as long of a wait list as we do, and we used to do, if and when the time comes that we all talk, me, the patient, the caregiver, and the primary oncologist, and say, “Look, I think now is time,” we’re able to make it happen. 

Katherine Banwell:

Yes. That’s a promising outlook to leave our audience with, Dr. Banerjee. Thank you so much for joining us today. 

Dr. Rahul Banerjee:

Absolutely. The pleasure was all mine. Looking forward to seeing many of you on a future episode of this. 

Katherine Banwell:

And thank you to all of our collaborators. To learn more about CAR T-cell therapy and to access tools to help you become a proactive patient, visit powerfulpatients.org.  

I’m Katherine Banwell.

Thanks so much for being with us today.  

Follicular Lymphoma Expert Q&A: Coping with Relapse and Managing Treatment Side Effects

Follicular lymphoma expert Dr. Kami Maddocks from The Ohio State University Comprehensive Cancer Center empowers patients and families with practical guidance on key aspects of managing follicular lymphoma. Dr. Maddocks covers effective strategies for managing treatment side effects, navigating the challenges of relapsed or refractory disease, and defining what survivorship means for both patients and their care partners.

Download Guide | Descargar Guía

See More from START HERE Follicular Lymphoma

Related Resources:

How Do Outcomes for Relapsed/Refractory Follicular Lymphoma Vary?

How Do Outcomes for Relapsed/Refractory Follicular Lymphoma Vary?

Addressing Vulnerabilities in Follicular Lymphoma

Addressing Vulnerabilities in Follicular Lymphoma

What Are Common Follicular Lymphoma Treatment Side Effects?

What Are Common Follicular Lymphoma Treatment Side Effects?


Transcript:

Lisa Hatfield:

Welcome to this START HERE Patient Empowerment Network program. This program bridges the expert and patient voice, enabling patients and care partners to feel comfortable asking questions of their healthcare team. I’m Lisa Hatfield, a cancer survivor and also an Empowerment Lead at Patient Empowerment Network. Joining me today is hematologist-oncologist

Dr. Kami Maddocks, Professor of Clinical Internal Medicine in the Division of Hematology at The Ohio State University Wexner Medical Center. Dr. Maddocks specializes in treating patients with B-cell malignancies, including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and chronic lymphocytic leukemia. Dr. Maddocks researches new therapies for these hematologic malignancies, largely through evaluating new targeted therapies in clinical trials. Thank you so much for joining us, Dr. Maddocks.

Dr. Kami Maddocks:

Thank you, Lisa. It’s a real pleasure to be here with everyone today and talking about follicular lymphoma, and I just really appreciate you having me.

Lisa Hatfield:

The world is complicated, but understanding your follicular lymphoma diagnosis and treatment options along your journey doesn’t have to be. The goal of START HERE is to create actionable pathways for getting the most out of your follicular lymphoma treatment and survivorship. Joining us are patients and care partners facing a follicular lymphoma diagnosis, some of which are newly diagnosed, in active treatment, watch and wait, and also living for years with their disease.

START HERE is designed to provide easy-to-understand, reliable, and digestible information to help you make informed decisions. I’m thrilled you’ve joined us. Please remember to download the program resource guide via the QR code. There is great information there that will be useful during this program and after. Okay, Dr. Maddocks, let’s start here. What is the latest in follicular lymphoma, and what are the most important highlights for patients and families?

Dr. Kami Maddocks:

When we look at some of the stuff that’s changed in follicular lymphoma, there has actually been some really exciting developments just in the last year in follicular lymphoma. So when you look at patients who have relapsed or refractory follicular lymphoma, we’ve actually seen the approval of three different new therapies just in the last year for relapsed/refractory follicular lymphoma. So one of those therapies, we saw a brand new approval, and that’s a therapy which combines an oral targeted therapy with a monoclonal antibody.

So the combination of the CD20 antibody, obinutuzumab (Gazyva), in combination with the BTK inhibitor zanubrutinib (Brukinsa) was approved in March of 2024 for patients with relapsed/refractory follicular lymphoma. And this was based on a study that compared that to the single agent anti-CD20 antibody. So while we have had CD20 antibodies approved in both original treatment for follicular lymphoma and relapsed disease, it was the first time that we’ve had a BTK inhibitor approved for the treatment of relapsed/refractory follicular lymphoma.

In May of 2024, we saw the approval of actually the third chimeric antigen receptor T cell or CAR T-cell therapy for relapsed/refractory follicular lymphoma. So previously, we’ve had two different CAR Ts that target the same antigen or protein CD19 on the cell. And the third therapy with the same target was approved in May of this year for relapsed/refractory follicular lymphoma. And then in June of 2024, we actually saw the approval of the second bispecific antibody for the treatment of relapsed and refractory follicular lymphoma.

So previously, we had one approved almost two years ago in December, and a second one, epcoritamab-bysp (Epkinly) was approved in June of this year for patients with relapsed/refractory follicular lymphoma. So three different treatments approved in this setting in the last year, which increases the options for patients. It also provides us with thinking about sequencing these agents. And there’s a lot of studies ongoing to decide or to think about what is the best way to sequence therapy, because there’s no right or wrong answer currently in which therapy did you choose and when in patients with relapsed/refractory follicular lymphoma.

And then thinking about managing when we’re choosing these therapies, what are the side effects of these therapies and managing these side effects? Right? Because chemotherapy is often used for patients with initial diagnosis, and there is very specific side effects to chemotherapy and ways to manage those side effects. But when we look at some of these newer therapies, we have to think about the different toxicity profiles that they have and how we manage those toxicities.

So when we’re thinking about the newer therapies, like bispecific antibodies and CAR T-cell therapies, there’s very specific toxicity with those therapies, including cytokine release or CRS. And then something called ICANS, which is immune effector cell-associated neurologic toxicities, which are neuro side effects of these therapies. And so how do we identify and manage those therapies and now even looking at ways to potentially prevent patients from having those specific toxicities.

Lisa Hatfield:

Okay, thank you. So regarding those toxicities, like the ICANS and the CRS, is there a difference in how you treat patients? For example, if a patient might experience those side effects, are they hospitalized for that type of treatment initially, or are all of these new treatments done on an outpatient basis?

Dr. Kami Maddocks:

Yeah, that’s a great question. So the answer can be variable depending on the specific product or the center where the patient’s receiving them, and then even the disease that they’re used in. So let’s just talk about bispecific antibodies to start. So the first bispecific antibody that was approved in follicular lymphoma was mosunetuzumab-axgb (Lunsumio). There’s no required hospitalization to administer that, but there is a recommendation that if patients have signs or symptoms of cytokine release.

So the primary symptom is fever. That’s the number one most common symptom that patients will get and how we define cytokine release. But patients can also have hypoxia or a drop in the oxygen or hypotension and a drop in their blood pressure. So if they have these, it’s generally recommended that they’re admitted for a period of observation to ensure that those toxicities don’t worsen or escalate and that they’re treated if they do.

Which treatment can include ruling out other causes. Some patients may need antibiotics if they have low blood counts and a fever. Some people will need fluids and oxygen. Then sometimes we use steroids like dexamethasone (Decadron) or even cytokine blockers to help manage those side effects, particularly if they’re what we call higher grade or more significant. The second bispecific antibody epcoritamab-bysp. That was previously approved in diffuse large B-cell lymphoma and there was a recommended hospitalization with a step-up dosing for that.

However, in follicular lymphoma, when they studied that, they gave an extra dose. So part of trying to prevent the cytokine release is giving a lower dose and then increasing the dose each week until you reach the maximum dose. So they added an extra kind of intermediate dosing in the follicular dosing and showed that that made a lower risk of…a lower number of patients had cytokine release. And that the majority of them had the lowest grade cytokine release.

So in follicular lymphoma, it’s actually with that increased one dose in there to get to the maximum dose. It’s actually not recommended, or it’s not required that patients are hospitalized for any of the doses. But, of course, if they would, same thing, if they would have side effects, then you would consider that. And then the same thing could be said for the CAR T-cell therapies. Some of them are given inpatient and then patients are monitored for a period of time, and then some are administered as an outpatient. And patients are seen daily for that to check on how they’re doing, monitor for side effects, have labs. And sometimes it just depends on the center administering the therapy, how they have a setup for patients to be monitored.

Lisa Hatfield:

So I have two follow-up questions to that overview. Are these newer approved therapies, are they available at some of the smaller cancer centers, or are they only available right now at the larger cancer centers or academic centers? Then my second question is, are they limited duration therapies or like bispecific antibodies, does that just continue until disease progression?

Dr. Kami Maddocks:

Yeah, those are great questions. So in general, if you look at the combination of the obinutuzumab and zanubrutinib that should be able to be administered anywhere, the therapy for the oral therapy is continued until progression. If you look at the bispecific antibodies, there’s both. There’s a time-limited therapy, and then there’s one continued until progression. I think in general, we’ve seen that initially these have been used at larger treatment centers, but now that they’ve been approved for a while, we have seen a lot of these being used at smaller cancer centers and in the community centers. Sometimes patients may receive their initial dosing at a larger center and then transition to a local center. But I think, like I said, now, especially the one that’s been approved for a while, we’re seeing that it can be started at many places.

Lisa Hatfield:

Thank you so much for that important overview, Dr. Maddocks. All right, it’s that time where we answer questions we’ve received from you. Remember, as patients, we should always feel empowered to ask our healthcare providers any and all questions we might have about our treatment and prognosis. Please remember, however, this program is not a substitute for medical care. Always consult with your own medical team. So before we dive into this Q&A, since this program centers on coping with relapse and managing treatment side effects, how do you approach these first-time conversations with patients and their care partners who are facing relapse and potentially dealing with a new set of side effects due to the changes in their treatment regimen?

Dr. Kami Maddocks:

I think that’s a great question, and I think there are a lot of things to consider. So I think the first thing that we want to think about when we’re talking about patients having relapsed or refractory follicular lymphoma is that just because patients have relapsed or refractory follicular lymphoma doesn’t always mean that they need treatment. So many patients, when they’re initially diagnosed with follicular lymphoma, are going to go through a period of observation or watch and wait where we know that they have follicular lymphoma, but they don’t have symptoms of their disease.

They don’t have a large number of lymph nodes involved, or their lymph nodes are not very large by the scans, and they don’t necessarily need to be treated until they become symptomatic or have certain concerns from their lymphoma that’s causing problems. So the same thing can happen probably more with relapse than necessarily refractory disease, but patients may…you may detect on scans that they have lymph nodes that are growing or that their disease has recurred, but they don’t always necessarily need to receive treatment.

Once you’ve identified that, yes, a patient requires treatment for their relapsed or refractory follicular lymphoma, the next thing to think about is that patient and their disease. So what age is the patient? What were they treated with initially? Because not all patients receive the same initial therapy. So the decision about what they’re going to receive when they relapse is going to be somewhat dependent on what they received for their initial therapy, what side effects they had from that therapy, and how they responded to that therapy.

The next thing is going to be that there is not just one option at relapse so really discussing the different options for those specific patients, and what are the options, what are the side effects of those options, what is the treatment schedule of those options? Because some treatments may have more toxicity, but they’re time-limited, whereas other therapies may be continued to help progression, they may have less toxicity, but over time that’s a toxicity that patients continue to experience on a daily basis.

So really talking to the patient about the options, what does the schedule of that treatment look like? Do they have to come in weekly? Do they have to come in once a month? And then again, the side effects and how that fits into side effects that they had with their initial therapy, how they tolerate that, are any of those side effects still there?  For example, if a patient has neuropathy from their therapy, that might be something that lasts and then considering all those things and making an informed decision with the patient.

Lisa Hatfield:

Okay, thank you. And these questions are in the perfect order, because we have a question from Lauren asking you, what is the difference between relapsed and refractory? 

Dr. Kami Maddocks:

Okay, this is another great question. I’m sure all these questions are great. When we think of relapsed disease, we think of a patient who’s had therapy, got in a response to that therapy, that response has lasted some time, and then their disease recurs. When we think of refractory, we think of that more as patients that have received a therapy, and they haven’t responded. Now, there is no standard definition of refractory. So we all agree that if a patient gets a treatment and their disease does not respond to that treatment, they’re refractory to that treatment.

But there’s no defined time for which if a patient has a treatment and responds to that treatment but has a short relapse, what’s really considered refractory. In general, a lot of studies that look at a therapy say that if you’ve had it, like if you’ve had rituximab (Rituxan) and you’ve relapsed within a six-month time frame, that that’s refractory. But some studies use three months instead of six months.

Lisa Hatfield:

Okay, thank you. Another patient, Jeff, is asking, Dr. Maddocks, I’m currently in an observation stage of non-Hodgkin lymphoma. I get blood work twice a year and scans once a year. I’m hoping it stays slow-growing. How long on average can a person live in observation mode before treatment must occur?

Dr. Kami Maddocks:

So this is another great question. And I’m going to provide kind of an overview that we’ll kind of set up, because there may be more questions like this. But in general follicular lymphoma is not one disease, which I’m sure since this is a program focused on relapsed/refractory follicular lymphoma, a lot of patients have heard this and know this. But it’s what we call it’s very heterogeneous, or it can behave very differently in patients, meaning that some patients will have very indolent disease, and then there’s a small portion of patients whose disease will be more aggressive.

We know that when we diagnose patients with follicular lymphoma there are some patients that are diagnosed and require treatment pretty quickly, whereas there are other patients that go many years, many, many years without requiring treatment. Some of that is because of the disease, and some of that is because of how we find a patient’s follicular lymphoma. Some patients, we don’t find it until they present with symptoms. Some patients find their own lymph nodes, and some patients are diagnosed because they have a baseline scan that for a totally different reason, maybe get into a car accident, have scans to make sure nothing’s broken, you find an enlarged lymph node, you biopsy it, and you find this diagnosis.

All that said, there are some studies that have looked at patients who are on observation or watch and wait and looked at treating patients who have what we call low tumor burden, or not a lot of lymph nodes, or not very large lymph nodes, but have what’s called advanced stage disease. So lymph nodes on both sides of the diaphragm, not large enough to necessarily require more aggressive treatment, they don’t have symptoms. But we’ve treated, we’ve looked at studies treating those patients with observation or watch and wait or single agent rituximab (Rituxan) therapy. And when you look at the patients in those trials, the median time to needing treatment for patients from observation was three years.

However, there were 30 percent of patients, so one out of three patients who were still being observed at 10 years without requiring any therapy. So there are patients, that’s almost a third of patients at 10 years who’ve been observed, not required therapy in that population of patients. And certainly I have been practicing for a while where I’ve seen patients, I do have some patients who’ve gone longer than that without needing therapy.

Lisa Hatfield:

Okay, thank you. And there you go, Jeff, we hope that you’re in that third. 

Okay, thank you for explaining that. Next question, I’m not sure if it’s Jeff Run or Jeffrey is asking about the most common side effects that are associated with bispecific antibodies, and what precautions can be taken to reduce the risk of infection?

Dr. Kami Maddocks:

Yeah, another great question. There are two different bispecific antibodies that are now approved for relapsed/refractory follicular lymphoma. And I will take this time to also say that some of the exciting ongoing work is looking at those agents in clinical trials, in the frontline setting, in combination with other therapies particularly non chemotherapies.In general, I would say similar side effect profile. The most common side effect between them is the cytokine release or the CRS. So that is the most common side effect. Again, this can be defined in different ways. The most common side effects that you see from that define CRS are fever, hypotension or low blood pressure, hypoxia or low oxygen, shortness of breath, chills, tachycardia or higher heart rate. 

We have talked a lot about CRS and what it entails and how it is defined and presents. But management, it depends on what we call grading. So for patients who just, who have a fever, oftentimes, number one, you want to make sure that it is CRS and that there’s not an underlying cause. So ruling out infection or coexisting infection, if a patient is neutropenic or has a low neutrophil count and is at high risk for infection, you may treat them with antibiotics with a fever while you rule out infection.

But oftentimes, if they have a fever, you can manage symptomatically anti-fever medications like acetaminophen (Tylenol). If a patient has worsening CRS and has other symptoms associated with it, such as the hypoxia, low oxygen, or hypotension, low blood pressure, then that’s when we escalate therapy. So one you direct treatment towards that. So if they need fluid, if they need oxygen, but then that’s when you’re thinking about starting medications such as the steroid medication. So we give intravenous dexamethasone, or there are certain cytokine blockers such as tocilizumab (Actemra) that can be given to help treat the side effects of the cytokine release.

Other common side effects or that we’re seeing in more patients in the clinical trials, fatigue, rash, and then infections including upper respiratory infections, and then COVID-19 infection as well. So part of treatment of these side effects is early recognition of the side effects. So patients are monitored closely and that you’re dealing with the side effects to help them from worsening. I think infection prevention is very important with these. So it’s recommended to consider prophylaxis for certain infections. So antiviral medication to prevent viral, such as shingles reactivation, medication to prevent a specific type of pneumonia, PJP pneumonia, and then consideration I think of just making sure that patients are up to date on vaccination. And if patients do have infection while they’re getting treated, potentially delaying treatment or taking a break in order for them to recover from treatment.

Lisa Hatfield:

Okay, thank you. And this person did not give their name but is asking, Dr. Maddocks, I wanted to know how to travel as safely as possible. Is it advisable to get certain vaccines for travel like yellow fever? I plan to travel to Europe via plane and cruise. They say that there’s stage III non-Hodgkin’s follicular lymphoma getting treatment every eight weeks.

Dr. Kami Maddocks:

So this is a great question, and I’m probably going to answer this a little bit more generically, because I think that it can depend a little bit as far as what specific vaccines. But when thinking about travel, I think that it’s a good idea to look at where you’re traveling because both, where you’re traveling time of year you’re traveling and what you’re going to do when you’re somewhere can depend on what vaccines are recommended. I usually advise patients to consider looking at the CDC guidelines for recommendations for what should be received in that area, travel that time of year, what they’re going to be doing.

And then sometimes there are places that will actually have a travel clinic. Once I know what vaccines are recommended, the patient knows what vaccines are recommended, then I usually work with them and pharmacy to decide what vaccines, if they can receive all those vaccines or if there were certain ones that we may not recommend. In general, it can depend on a patient, what treatments they’ve received or if they’re actively receiving treatments. But in general, we like to avoid live virus vaccines in our patients. So I take into all those factors and then would recommend discussing the specifics with your physician.

Lisa Hatfield:

Luca is asking what are the long-term side effects of bispecific antibody treatment, and how will I be monitored for them after treatment ends?

Dr. Kami Maddocks:

So another great question. I think, when we think about the side effects in general, the bispecific antibodies in the CAR T both have those unique toxicity, cytokine release being the most common. And then you also have worry about the neurological toxicity. The difference is that, depending on the specific, bispecific or CAR T that you use, but we usually, typically see these occur in lower grade or not as severe with a bispecific antibody than you can see with a CAR T-cell therapy.

You can still have cytopenias and infection risk with these therapies. Whereas in chemotherapy, we think of that as more generalized toxicities, with the cytopenias, with the risk of infection with the GI toxicities. When we think about long-term side effects, so I think one of the important things to recognize is that bispecific antibodies have not been around that long in the scheme of things, though we can’t say, the risk of 20 years, what do we see or even 10 years.

But when we think about what we have seen, we’ve seen things like the cytokine release, the infections, the cytopenias, but what we haven’t seen is things like the secondary malignancies that we worry about when we think about chemotherapy or even maybe immunomodulatory therapy or secondary cancers that patients can develop. I think for long-term monitoring, right now, at least the biggest thing you want to think about is that these therapies do deplete the lymphocytes, for a prolonged time. And so the risk of viral infections or reactivation of infections, and making sure that’s being considered.

Lisa Hatfield:

Okay, thank you. That’s an important question. So another may possibly be a care partner, Marilyn. How can I best support my loved one during relapse and what should I do if I notice my husband with new or worsening symptoms?

Dr. Kami Maddocks:

So another great question. I think it’s first of all important to ask the physician about what symptoms to watch for. So you know, are there certain worsening new symptoms or worsening symptoms that seem more likely to be related to follicular lymphoma versus something else. I think it’s always important to encourage your loved one if they are experiencing new symptoms to reach out to the physician so that they can be evaluated. Because follicular lymphoma is a disease that many people live with and many people live with it for many years. We know that patients can experience other things.

Not everything is going to be just because of the follicular lymphoma. So it’s important to be evaluated, and recognize what is going on and what is attributed to the follicular lymphoma. I think being supportive, thinking of questions to ask and making sure that those questions are answered. I think thinking about, are there resources available? I think educating yourself is one of the most important things that people can do. So knowledge is power. So just participating in things like this I think can be very helpful, because learning about what’s out there, knowing that there are many options, I think being supportive and having a positive attitude, are all helpful things.

Lisa Hatfield:

Okay, thank you. So we have another big and important question from Aubrey. How can I live a full life with follicular lymphoma while managing the emotional toll of knowing the disease may relapse? And what lifestyle changes or habits should I focus on to maintain my health during remission?

Dr. Kami Maddocks:

Yeah, so this is another great question, and I think there’s probably lots of different ways to answer this or lots of different things to consider. So I think in general, as we’ve talked about follicular lymphoma is something that people live with for a long time. So thinking about just your general health and general disposition. So, we want to think about incorporating exercise, incorporating a healthy lifestyle, thinking about exercise, and being physically active.

Thinking about particularly diet and not saying that there’s any food that you need to avoid or any specific thing, but I think eating healthy is important. I think sleep hygiene is, can be very critical for patients. I think finding, and then just general health, it’s good to have a PCP so that you’re getting good routine health maintenance. We have to think about making sure that we’re managing other medical things like blood pressure, glucose, looking, doing other routine cancer screenings, depending, if somebody’s male or female, but the screening that’s recommended for that.

Now when we’re thinking about managing this does take an emotional toll because a lot of times, when somebody’s initially diagnosed, if they don’t need treatment, the question is always like, well, how long am I, is it going to be before I’m going to need treatment? How am I going to tolerate that treatment? How long is that treatment going to last? And then that resets once a patient’s had treatment. Well, how long will I stay in remission for this treatment? What’s going to be next?

I think things that can help with that are, sometimes I think involving like psychosocial oncology, I think support groups, I think that it’s very beneficial for many patients to talk to people, whether it be through a u look at the median age at diagnosis is in the 60s, and median overall survival is greater than 20 years. So many patients are going to live with this more like a chronic disease. And so learning to kind of knowing basic facts on what it is, what are the treatments that are available, what do those treatments look like, what are the reasons that you need those treatments? And that you are able many times in those periods of not needing treatment to live a very normal lifestyle and do things. I think making sure that, I think it’s important.

One thing that I think can be helpful is you’ll continuously follow up with your physician. So thinking about questions and concerns that you have throughout the period of time, writing them down that gets them out of your mind on paper. And then when you go to see your doctor next, you have that list of questions. Because I think, sometimes we think about things, and then we worry, worry, worry. But putting them down on paper or even sending them through like a secure MyChart email message and then talking them out, because a lot of times if you don’t do that, then when you go to see your physician you think, oh, I don’t really have any questions.

And then you leave and you’re like, oh, I should have asked these 10 different things. So again, I think asking for resources. So there are many different patient friendly resources out there. I think reading material that’s been written or vetted by medical professionals as opposed to just any random material can be very helpful for patients. And then again sometimes seeking out kind of peer support.

Lisa Hatfield:

Okay, great, thank you. Sean is saying that he was diagnosed with follicular lymphoma in 2022 and in an active treatment. What advice do you have for someone transitioning from patient to survivor? I am eager and fearful.

Dr. Kami Maddocks:

Awww. Well, another good question. And I think one thing I want to recognize is that somebody with cancer is defined as a survivor from the time they’re diagnosed moving forward. So you’re already a survivor. But when you, I do think, and I tell patients this, even when we’re talking about starting treatment, I do think that being aware of kind of where patients are at mentally is important.

Because when you go through, when a patient goes through treatment, they’re very focused on next steps and next steps when you’re going through treatment are, when’s my next treatment going to happen? When’s my next scan going to happen? When you get to that point, when you’re done with treatment, you no longer have those small milestones that you’re reaching the next treatment, the next scan. You now are like, oh my gosh, I had this treatment and now, how long is it going to last?

What’s going to happen to me? What else can happen to me? And there can be a lot of fear and anxiety. I would first tell you that’s totally normal. That is a normal feeling to have at this point. So I think one, recognizing that you have them is important. I think considering things like we’ve talked about, is there a survivorship clinic, is there psychosocial oncology? Is there something that might help in talking those things out? I think setting up milestones, what is the next thing? I’m going to have a three-month appointment, I’m going to have labs.

These are the things I need to be thinking about, but if I’m not noticing these also, what things can I do to return to the things I like to do. I think also I would go back to saying, I think this is where just thinking about getting good sleep, getting exercise, eating a healthy, balanced diet, and then socializing and making sure that you’re involving friends and family.

Lisa Hatfield:

Okay. Thank you. And, Sean, you’re already a survivor, Dr. Maddocks said so. So good luck, Sean. All right, Dr. Maddocks, thank you so much for being part of this Patient Empowerment Network START HERE program. It’s these conversations that help patients truly empower themselves along their treatment journey. On behalf of patients like myself and those watching, thank you so much for joining us, Dr. Maddocks.

Dr. Kami Maddocks:

Well, Lisa, thank you so much for having me. It’s been a real pleasure, and I hope everybody has a great day.

Lisa Hatfield:  

Thank you. I’m Lisa Hatfield. Thank you for joining this Patient Empowerment Network program.


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Current and Emerging CAR T-Cell Therapies for Myeloma

What are the current and emerging CAR T-cell therapies for myeloma? Nurse practitioner Donna Catamero discusses approved CAR T-cell therapies for multiple myeloma, who they’re appropriate for, ongoing research to expand their use, and treatment options if the disease returns after CAR T-cell therapy.

Donna Catamero is a Nurse Practitioner and associate director of the Multiple Myeloma Clinical Research Program at Mount Sinai Hospital in New York City. Learn more about Donna Catamero.

See More From Thrive CAR T-Cell Therapy

Related Resources:

Undergoing CAR T-Cell Therapy? Why Managing Overall Health Is Essential

Undergoing CAR T-Cell Therapy? Why Managing Overall Health Is Essential

Being Empowered | The Importance of Understanding Myeloma

CAR T-Cell Therapy Support | Questions to Ask About the Process

CAR T-Cell Therapy Support | Questions to Ask About the Process

Transcript:

Katherine Banwell:

Donna, welcome. Thank you so much for joining us. Would you please introduce yourself and tell us about your role at Mount Sinai? 

Donna Catamero:

Sure. I’m Donna Catamero, I’m a nurse practitioner, and I’m the associate director of the Multiple Myeloma Clinical Research Program at Mount Sinai Hospital in New York City. 

Katherine Banwell:

Would you tell us about the currently approved CAR T-cell therapies and which myeloma patients they may be right for?  

Donna Catamero:

So, currently, we have two products available for patients. The first is idecabtagene vicleucel (Abecma), and it’s approved for patients with relapsed/refractory disease who have received two prior lines of therapy, and this includes exposure to an immunomodulatory agent, so, your lenalidomide (Revlimid), your pomalidomide (Pomalyst), a proteasome inhibitor, and that includes Velcade/Kyprolis, and an anti-CD38 monoclonal antibody, so this is your daratumumab (Darzalex) or isatuximab-irfc (Sarclisa). 

The second product we have to offer patients is ciltacabtagene autoleucel (Carvykti), and this is approved for patients a little bit earlier on, so, also relapsed/refractory disease who have received at least one prior line of therapy, and it must have included proteasome inhibitor and an immunomodulatory agent, and they need to be refractory to Revlimid. So, what “refractory” means is they relapsed while taking the Revlimid.  

And both these therapies are important for patients, so if patients are inquiring about CAR T therapy, they should ask their providers what product is available for that. 

Katherine Banwell:

Let’s talk about research in CAR T-cell therapy. What new options are being studied, and how far along is the research? 

Donna Catamero:

So, we’re actually very excited. So, the two products, Abecma and Carvykti, we’re actually looking at them in newly diagnosed myeloma patients, and this is regardless of if patients are eligible for transplant or not, and we’re looking at comparing transplant versus CAR T therapies, so we’re hoping to move CAR T therapies for newly diagnosed – so, first-line therapy – so this is very exciting, and we’re also investigating new products with dual targets. 

So, right now, our two approved CAR Ts, they target BCMA, so now we’re looking at CAR Ts that are targeting BCMA and another target – so, GPRC5D or CD19 – so this means that the CAR T is grabbing onto more cells, so, in theory, it would have a higher cell kill.  

And then, we’re also investigating CAR Ts that we call off-the-shelf, so, autologous CAR Ts, so, donor CAR Ts, and this is actually exciting for patients who maybe can’t wait for manufacturing of their T cells, and now we can use donor T cells. So, these are earlier on studies, so we’re hoping within the next few years, more options will be available for patients.  

Katherine Banwell:

Yeah. What happens if the myeloma comes back after T-cell therapy? What are the treatment options available beyond CAR T? 

Donna Catamero:

Earlier on, we were hoping that CAR T would be our cure, but patients are getting very long, durable remissions from their CAR T therapy. We see patients who are five, seven, eight years out from their CAR T therapy, so patients do have a long time in remission, but the myeloma can come back. 

And what do we do with these patients? We actually have been very successful managing patients post a CAR T relapse, so we are looking at bispecific antibodies, which were recently approved over the past several years, and we see patients who have had relapses from their CAR T go back into a remission with these bispecific therapies, and again have long, durable remissions. So, we can absolutely manage patients if their myeloma comes back after CAR T therapy. 

Myeloma Support and Resources | Why It’s Essential to Voice Your Concerns

Myeloma Support and Resources | Why It’s Essential to Voice Your Concerns from Patient Empowerment Network on Vimeo.

Why should you speak up when it comes to your myeloma care? Dr. Sikander Ailawadhi discusses the importance of sharing issues with your healthcare team in order to access support and resources that can help. 

Dr. Sikander Ailawadhi is a hematologist and oncologist specializing in myeloma at Mayo Clinic in Jacksonville, Florida. Learn more about Dr. Ailawadhi.

Related Resources:

Accessing Quality Myeloma Care | Advice for Overcoming Obstacles

Accessing Quality Myeloma Care | Advice for Overcoming Obstacles

Key Advice for Myeloma Patients | Questions to Ask About a Care Plan

Myeloma Symptom Management | An Expert’s Approach

Myeloma Symptom Management | An Expert’s Approach

Transcript:

Katherine:

I would like to talk more about self-advocacy, Dr. Ailawadhi, managing the worry associated with a diagnosis, concerns about relapse, side effects. It can lead to emotional symptoms like anxiety and fear for many. So, why is it important for patients to share any worries they’re having with their healthcare team?   

Dr. Ailawadhi:

Yes.  Extremely important. See, nobody’s thinking, “Okay, I’m going to have cancer today.” Nobody’s prepared for it ever. Cancer is always a diagnosis that comes out of the blue, blindsides us, and then suddenly we have to change the rest of our life because of it.  Not only our life, our caregiver’s life, family’s life, everything changes.  

So, it is okay to admit that it is difficult. It is okay to admit that we need help. And, Katherine, I like your kind of the use of the word, self-advocacy, although I want to qualify it.  

A lot of times we say patients got to be their own advocates. But if a patient doesn’t know what to ask, they’re going to be lost. My thought is it is okay to – the first and foremost that a patient or their caregiver can do is please report your symptoms or how you’re feeling.  And those symptoms could be physical, those could be psychological.  Please report what are you feeling, what are the symptoms. On a drug, what are the side effects, et cetera, so that your healthcare team can try to address them. Don’t ever assume, “I am on chemotherapy. I should have diarrhea.”  No. Don’t think, “I’m on chemotherapy. Other patients outside in the waiting room look sicker than I. I feel embarrassed to ask a question.”  

We hear this so many times. A lot of patients will say, “I feel embarrassed to ask that I’m going through this symptom, because I see sicker people outside.” Yeah, but know when I’m with you as a patient, you are it. I’m not thinking about anybody else. And I don’t want anybody else’s decision to obscure or cloud our relationship at that visit.  Please report your symptoms. Please ask for help. 

To me, that is good enough self-advocacy. Self-advocacy is not saying, “I should get this treatment, not that treatment.” But self-advocacy could mean, are there clinical trial options?  I know I live far away from a large center. Could I get a tele-visit with a large center? Could I get a second opinion from someone? Those are all very, very reasonable questions, and by asking those questions, a patient is advocating for themselves.  

Katherine:

As you alluded, there’s a whole healthcare team working with each patient, and there’ll be people on that team who can help support a patient’s emotional needs.  So, one thing that’s on the mind of many viewers is the financial aspect of care. And you mentioned that earlier everyone’s situation is different, of course, but where can patients turn if they need resources for financial support?  

Dr. Ailawadhi:

Very important question. I can tell you every day when I come into my office, my nurse has a stack of documents ready for my signature.  Every single day. Today, there was only one, but there could be different numbers. And these are generally from foundations from diagnosis confirmations, et cetera. Things that we are filling on and signing on behalf of our patients so that they are able to receive resources, whether it’s from a pharmaceutical manufacturer, a foundation, or society that has funding available, et cetera. I should start by saying, Katherine – and I feel embarrassed to admit this, but I should start by saying, I may not have all the answers for my patient during that visit.   

But I think the very important piece where we can start is asking the patient, “Is this causing any financial strain on you?”  As I mentioned earlier, we don’t think about, “Oh, I’m going to have cancer today. Let me prepare for that.” Or “I’m going to have cancer five years down the road. Let me prepare for that.” We’re not always ready for this. It’s okay. It’s important for me to ask if there is a problem, and it’s important for the patient to admit there’s a problem or say, “Well, I’m having difficulty with copayments.” And whatever may be difficult for one may be okay for the other. So, I shouldn’t assume.  So, that discussion must happen.  

Generally, in our setup, what happens is if the patient brings up a concern, if I identify a concern, or if we think something may be going on, but we’re not very sure about it, we tend to bring in our social workers. The social workers are typically the ones who are able to do that discussion with the patient, talk about what are the resources available. What are the foundations that we can apply to?

We have patient navigators who can do the similar things. So, the patient navigator, social worker, there are different individuals who will be able to provide much more granular information. I also strongly suggest patients to join support groups.  

There are lots of resources, which I may not be aware of during our visit with a patient, but I can connect to the social worker, their patient navigators, and online support.    

What’s Next in Myeloma Research and Treatment?

What’s Next in Myeloma Research and Treatment? from Patient Empowerment Network on Vimeo.

What are the next generation myeloma therapies? Dr. Krina Patel shares an update on new agents, such as CelMoDs, and discusses how combination treatment and sequencing of therapy will evolve in the future of myeloma care.

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.

See More from Evolve Myeloma

Related Resources:

Next Generation Myeloma Treatment Options

Next Generation Myeloma Treatment Options 

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy 

Evolving Myeloma Treatment Options | CAR T-Cell Therapy

Evolving Myeloma Treatment Options | CAR T-Cell Therapy 

Transcript:

Katherine:

Dr. Patel, for the last few years advances in myeloma treatment have been focused on the cellular therapies like CAR T. Can you share what’s next in myeloma research and treatment? 

Dr. Krina Patel:

Yes, I think it’s been really exciting. The last 10, 15 years, really, we’ve just catapulted in the whole world of immunotherapies; so, from monoclonal antibodies to even IMids and CelMoDs and things that we’ll talk about a little bit now, and cell therapy as well as just other ways of engaging T-cells with the bispecific therapies too. So, I think what’s really exciting, that we have not just new mechanism of action that’s coming down the road but new targets.  

So, again, coming back to really the big stuff like immunotherapy that I really like a lot and what I really am excited about, we have different ways of using the immune cells to help fight myeloma.  

And so, things like IMids, lenalidomide, and pomalidomide that are older drugs that we’ve had since 2006, but really there’s newer ones called CelMoDs that are coming out that are being evaluated in clinical trials. One is called iberdomide. Another is called mezigdomide.  

So, we’re really excited about this really in combination therapy, just like the prior iMids were used. And what it really does is it improves your immune system; it activates it to a point where things like monoclonal antibodies, such as daratumumab or isatuximab or elotuzumab, can work better in synergy.  

But even new trials with some of our CAR Ts that we already have available, the BCMA therapies, combining it with these to see if we can make those T-cells work better. 

So, once you get the CAR T-cell infusion, can we give some of these therapies now to improve how long it lasts, how well they work. And the same thing with the bispecifics.  

These are therapies that are using the T-cells that are already in your body. Can we combine it with some of these of other immune therapies that will help the T-cells already there get activated, and then the bispecific takes them to the myeloma to really get treated. And I think those combination studies that are coming down are really, really exciting. And then, I think the new antigens, as I mentioned, not just BCMA therapy but we have GPRC5D and we have something called FcRH5.  

And to my patients, I say it’s alphabet and number soup basically but they’re really targets for myeloma that we’re finding. It’s pretty amazing, considering that we didn’t have a target for the longest time, like lymphoma when they had their CD19 and we were jealous. And now we’re finding all these targets and now we’re figuring out how do we combine different mechanism of action for different targets so that we can hopefully kill every last myeloma cell.  

Care Partners | What Should You Know About the Bispecific Antibody Treatment for Myeloma?

Care Partners | What Should You Know About the Bispecific Antibody Treatment for Myeloma? from Patient Empowerment Network on Vimeo.

What are care partners essential when a loved one is undergoing bispecific antibody therapy for myeloma? Nurse practitioner Alexandra Distaso from Dana-Farber Cancer Institute explains the bispecific antibody process, reviews potential patient side effects, and shares resources that can help support care partners.

Alexandra Distaso, MSN, FNP-BC is on the Multiple Myeloma Nursing Team at Dana-Farber Cancer Institute.

Download Resource Guide

See More from the Care Partner Toolkit

Related Resources:

What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

What Myeloma Patients Need to Know About Bispecific Antibodies

What Myeloma Patients Need to Know About Bispecific Antibodies

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy

Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell.

Being a care partner can be a demanding role. From understanding a loved one’s diagnosis to participating in treatment decisions, navigating care with a loved one can be challenging. That’s why the Patient Empowerment Network created the Care Partner Toolkit series to provide care partners with advice and information so that they can feel empowered and confident during the process. In today’s program, we’re going to learn about bispecific antibodies, how this myeloma approach works, who it’s right for, and the important role that care partners play throughout the process.

Before we meet our guest, though, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access the guide to help follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help you plan future webinars. And finally, 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 our guest, nurse practitioner Alexandra Distaso. Alexandra, welcome. Would you please introduce yourself?

Alexandra:        

Hi, Katherine. Thank you for having me. Yes, my name is Alexandra Distaso. I am a nurse practitioner at Dana-Farber Cancer Institute in Boston. I’ve been a nurse practitioner for just about nine years, and I’ve been at Dana-Farber for eight of those years.

Katherine:         

Well, thank you so much for joining us today. I’m looking forward to having a discussion with you. Alexandra, you work with myeloma patients and their care partners on a regular basis. What is your role on the healthcare team?

Alexandra:        

Yeah, so as a nurse practitioner, I’m seeing patients every day in the clinic that I’m here. And we’re seeing patients for both their kind of monthly check-in visits prior to treatment, sick visits, symptom management visits. So, either that’s once a month for your routine visit, or a couple of times a month if you’re going through a transition of treatment or having some sort of side effects we need to work on a little bit more closely.

Katherine:         

Well, as I mentioned today, we’re going to be focusing on bispecific antibody therapy. It’s a relatively new approach. What is it exactly?

Alexandra:        

Yeah. So, bispecific antibodies are a really exciting new therapy in myeloma that we’ve had for within the last year.

So, we have three bispecific antibodies that are currently approved right now. And the way that they work is, the medication binds to the tumor site on your plasma cell, where the myeloma cell is, and it binds to a T cell, which is your immune system cell. And it kind of works to redirect the T cell, your immune system, to kill off the cancer cells in your body.

Katherine:         

Okay. How has this treatment impacted the state of myeloma treatment and care?

Alexandra:        

This has been a great option for patients who are now triple-class refractory and further into their myeloma journey. The development of these new drugs represents really kind of a new era in myeloma. We’re having a lot of patients who are now exposed to more therapies with using three or four drug therapies in the first-line setting. So, having an extra line of therapy now further down the road has been a great option for a lot of patients.

Katherine:         

Well, who is this treatment approach approved for, and what are the eligibility requirements?

Alexandra:        

So, one thing that’s great about bispecific antibodies is that there is not a lot of restriction on who we can use these therapies for. So, these are great for patients who are a little bit more frail or maybe aren’t up for something like a CAR T, or whose disease is a little further along, and they don’t have time to wait for something like CAR T, which requires collecting of cells and manufacturing. What’s great about these medications is that they’re off the shelf. They’re ready to go kinda when you need them. There are restrictions in terms of how many lines of therapy that you need to have had before you can currently get bispecifics.

So, right now, you need to have four prior lines of therapy, and that needs to include an immunomodulatory agent. So, something like a lenalidomide (Revlimid) or a pomalidomide (Pomalyst), a proteasome inhibitor like bortezomib (Velcade), and a monoclonal antibody like daratumumab (Darzalex) before you’re eligible for these.

Katherine:         

Have there been any recent bispecific antibody research developments that patients should know about?

Alexandra:        

So, there are at least three bispecific antibodies that are hopefully coming into approval in the next several months to year, cevostamab being one of them. It’s a very exciting time for myeloma with all of these medications being approved. Teclistamab (Tecvayli), elranatamab (Elrexfio), and talquetamab (Talvey) in the last year. There’s still a lot of research on bispecific antibodies, especially trying to bring them all outpatient instead of just having inpatient treatment, and in addition, looking at them with other medications, such as teclistamab with daratumumab.

Katherine:         

Okay. Well, thank you for that, Alexandra. This gives us a good idea of what the therapy is, and how it works to treat myeloma. So, let’s dive into the process. How is this treatment administered, and what’s the frequency?

Alexandra:        

So, currently, all of the bispecifics are given as subcutaneous injections.

And all of them do require a current hospitalization visit, somewhere between four and 10 days, depending on which medication you’re getting and what schedule you’ll be on. So, everyone is required to be in the hospital. Again, we’re trying to move that outpatient to minimize patients’ times in the hospital if we have to. And you get a lower dose with that first exposure to each of the medications, and then we build up the dose for the doses in the hospital into what will eventually be your outpatient weekly, or biweekly dosing.

Katherine:         

Okay. Are there only certain medical centers that have this therapy? How widely available is it?

Alexandra:        

So, right now, the step-up dosing, the inpatient hospitalization part of bispecifics is primarily only at academic medical centers. So, it is a little bit more restricted in that initial therapy. But what we are seeing is that a lot of the community practices are able to enroll and give these medications in the community.

So, some patients will come see us for a consult and the initial step up, but then they’re able to go back to their primary team after the first cycle so that they’re not commuting back and forth to Boston all the time.

Katherine:         

That’s good to know. So, once the therapy has been given to a patient, what happens next?

Alexandra:        

When you’re admitted for these initial step-up dosings, we closely monitor you for reactions in the hospital. That’s why we kind of are doing this in in-patient settings to monitor very closely for CRS and neurotoxicity, which we’ll talk about a little bit later. While you’re in the hospital, they’re checking your labs every day, they’re monitoring your vital signs, they’re doing silly questions like, “Do you know your name and the year,” to kind of monitor how you’re functioning. Once you have passed kind of the step-up dosing, either you’ll come back to me and your primary team at Dana-Farber, or we’ll communicate with your local team to set up your schedule for moving forward.

Katherine:         

What are the short-term side effects associated with bispecific therapy?

Alexandra:        

Yeah. So, the short-term side effects that we’re watching for are these reactions in the hospital called CRS, cytokine release syndrome, and neurotoxicity.

So, the CRS is an inflammatory response where cytokines are released and usually cause a fever. We monitor and make sure that the fever isn’t being caused by some sort of infectious process or there’s no other cause for the fever. And if not, then there are medications we can give to help reverse these side effects while you’re in the hospital.

So, the way that we treat that is, again, we’ll make sure that there’s no sort of infection or other reason for a fever. And if the patient continues to have the fevers and they have low blood pressure and changes in their oxygen needs, which is kinda what happens if this inflammation progresses, is we’ll give things like dexamethasone, a steroid, or another medication called tocilizumab to help kind of reverse the effects of the cytokine release.

Katherine:         

Who else is on the healthcare team when someone receives these therapies?

Alexandra:        

Yep. So, you’ll always meet with your oncologist or an oncologist at the academic medical center where you’re going to be getting the medication to go over potential side effects, what the treatment entails, and consent. We have nurses here that are specific to bispecific antibodies, that help coordinate with your local team if you’re going back to your local practice. We have the infusion nursing team who are the ones who are actually giving the bispecific antibody therapies. They explain kind of what to watch for at the site where the injection goes. And then we have pharmacists who are also available to meet with you and go over any questions you may have about the treatment.

Katherine:         

What do we know about long-term side effects? Are there any?

Alexandra:        

So, long term, what we’re really seeing is risk for infections. So, all of these medications lower your blood cell counts, and we have to watch for these opportunistic infections, fungal, bacterial, viral.

Which is why it’s important that we have everyone on supportive medications to try and prevent that from happening. But long term, that is certainly something that we’re seeing. With the talquetamab, there can also be some skin and taste changes, and those are not necessarily right at the inpatient dosing, but we can see that. But those are things we’re also managing in the months after the initial therapy.

Katherine:         

Okay. Why is it so important that care partners let the healthcare team know of any changes that they see in their loved ones?

Alexandra:        

I say this to my patients and their families all the time. They know their family member best, and they may be one to notice that they’ve been more tired, or their energy just isn’t the same, or they do have a little cough that maybe the patient hasn’t even really noticed. And those are all things that we want your observation, we want you to speak up about, because the sooner we address some of these problems, the less complications the patients may have.

Katherine:         

What are the supportive medications for somebody who might be having side effects?

Alexandra:        

Yeah, so with the talquetamab, which we’re primarily seeing a lot of skin side effects and mouth discomfort, a lot of the time we have special mouthwashes to prevent discomfort and irritation. Things like biotin to just keep the mouth moisturized. Steroid creams and nail ointments to help with sometimes some peeling of the skin. And then for all bispecifics, we have everyone on viral prophylaxis. Something like acyclovir (Sitavig or Zovarax) or valacyclovir (Valtrex). PJP prophylaxis. So, something like sulfamethoxazole and trimethoprim (Bactrim) or dapsone (Aczone). And almost all of our patients are on an IVIG infusion once a month to help support their immune system and prevent against infections.

Katherine:         

Alexandra, you mentioned care partner looking for a cough, for instance, in a patient. What other things should care partners be looking for?

Alexandra:        

Any kind of change in the patient’s baseline is always helpful to know. So, if people are feeling much more tired, even if you’re not due for your therapy, sometimes calling to say that they just don’t seem themselves, we can check their blood counts. And again, sometimes they might need a blood transfusion, or their white count might be quite low, and they might need some Neupogen or filgrastim to help kind of support their blood counts. So, really kind of notifying us, even if it doesn’t seem like a big thing, it’s always better to call.

Katherine:         

Yeah. How long will a patient be on a therapy like this?

Alexandra:        

So, we still don’t know exactly the long-term duration of response. I think the most recent update we have was a median of 18 to 22 months was the last report. Which is a great response for what we have in myeloma.

Katherine:         

So, does the length of time a patient is on a therapy depend on the patient themselves, their comorbidities, et cetera?

Alexandra:        

Sometimes they’re comorbidities, but it is usually more just how their myeloma responds. So, every month when you’re coming in for therapy, even if your therapy is weekly or biweekly, every month, we’re monitoring your myeloma markers, and every month we’ll go over those markers to make sure we’re still seeing a good response. Usually, we’ll do a PET scan or a skeletal survey to also monitor everyone’s bones and any other lesions, they may have.

Katherine:         

What is considered an ideal response?

Alexandra:        

An ideal response. A lot of times we’re seeing everyone’s light chains go to even an undetectable level. So, even if we see some partial responses where the light chains were, let’s say they were 100 and they’re going down into the normal range, that’s still wonderful.

If it stayed like that for months, we wouldn’t make any changes. But best-case scenario, we see them go to a level that we can’t detect them in the blood work.

Katherine:         

As I mentioned, Alexandra, this program is aimed at helping care partners understand the process and how they can support their loved ones. What do you feel is the care partner’s role?

Alexandra:        

I feel like the best way for care partners to support patients is to kind of take the time to learn about the myeloma and the therapy and try to do the best they can to just be there for not just moral and emotional support, but the other little things that they may need. Coordinating rides, if it’s a family member, asking friends for help.

And then other things like insurance phone calls can be incredibly time-consuming and taxing. Or waiting at the pharmacy to pick up medications. Any, even little things like that, I think take a huge load off the patients who are doing this day in and day out.

Katherine:         

Yeah. Are there key questions that care partners should ask as they begin the process?

Alexandra:        

I think the best thing that patients and caregivers can do is if they have questions prior to the visit is to make a list. ‘Cause, I’m guilty of this myself, as soon as I show up at my doctor’s office, I completely forget what I wanted to say. So, making a list prior to the appointment, I think, is hugely beneficial. And then I don’t think that it’s ever a bad thing to ask for the doctor or nurse practitioner or pharmacist, whoever you’re meeting with, to see if they can repeat themselves. We’re putting a lot of information into a very short period of time.

And to try and keep track of, again, schedule, supportive care medication, when you’re going to need to be in the hospital, how long, what your follow up will be, taking notes during the visit or asking to hear it again is always helpful. Not even just for the caregiver, but sometimes for the patient who’s still trying to wrap their head around some of the change in therapy.

Katherine:         

Right. Yeah. That’s really good advice. As we’ve covered, it’s not always easy being a care partner. What would be your best advice for those who are caring for someone undergoing bispecific antibody treatment?

Alexandra:        

I would say it’s hard to put out how important care members are to the entire care team. Again, not just for the logistical, getting the patients to appointments, getting their medication, but really having someone the patient feels comfortable to be able to lean on. And again, they may say, “I’m so overwhelmed in these visits, and I really need some help.

Could you ask these things?” Helping them keep track of all these medication changes and appointments and visits and any sort of even small things like grabbing them a water so that they’re staying hydrated. Those little things make such a difference to people. And I think doing those things, no matter how small they feel, really helps support the patients through these changes in therapy.

Katherine:         

Besides yourself, what other staff members can care partners turn to for support?

Alexandra:        

So, at our office, we have an amazing group of triage nurses who are available Monday to Friday all during office hours. We have after-hours. If your patient or family member spikes a fever and you’re worried they just don’t look good, there’s always a doctor on 24/7 that you can page to kinda ask for advice and see what to do from there. And again, we have infusion nurses who are giving these injections every day.

And they are wonderful resources on what you might feel later in the day, what that site might look like, side effects that might pop up. So, really, anyone wants to be there to answer questions to make it easier for the patient or the family.

Katherine:         

Are there social workers or psychologists on the team as well?

Alexandra:        

Yes. We have an amazing group of social workers at Dana-Farber. And one thing that I really like about the way our program is run is that we have a social worker who is dedicated specifically to myeloma. So, they’re very familiar with these medications and the hospitalization requirements, which can be extremely tough. And so having resources and just someone to talk to, both through social work and our psychosocial oncology department, is also a wonderful resource to have.

Katherine:         

What about online resources? Do you have any recommendations?

Alexandra:        

So, I think that the IMF, the International Myeloma Foundation, and the NCI, have amazing resources for patients.

Actually, the IMF has an entire caregiver support page with kind of caregiver self-help, and ways that you can care for the patient. Care for the caregiver, and care for the patient. I think the MMRF has wonderful resources, and they also have a lot of online forum videos about bispecific antibodies and the different treatments for myeloma that are available if you want to learn more. And then same thing with The Leukemia & Lymphoma Society. Excellent resources online.

Katherine:         

Thank you so much for all of that. What about self-care for the care partner? Why is that so important?

Alexandra:        

I feel like this is such a hard thing for people because it always gets put on the back burner. And I know a lot of the times it’s like when you’re on an airplane and they say, “Put your oxygen mask on yourself before you put it on anyone around you,” because you can’t help others if you’re running on empty. You really need to take care of yourself.

Make sure you’re not just functioning, that you’re eating and sleeping and hydrating and taking care of all your own personal needs, but also that you’re taking time for you to kind of reflect and have some time to decompress from everything you are trying to do to help your family member or loved one.

Katherine:         

Why should care partners speak up and ask questions about how they’re taking care of the patient, what they can do to help the patient and themselves?

Alexandra:        

Yeah, I think that these bispecific antibodies are new, and one great thing about them is that overall they are really well-tolerated in general. So, hopefully, it means the patient is feeling pretty good and having a really nice response to their therapy. But if they’re not feeling good, we want you to speak up at home. Again, sometimes patients are the last person that want to tell you there’s a problem ‘cause they’re worried about missing their therapy.

And I always tell patients it’s sometimes not safe, if you do have a cough, if you had had a fever, we want to be safe and maybe hold a dose of therapy to address maybe something else that’s going on and avoid further complications another week. So, if you’re noticing something, I always encourage people to speak up and let us know of any concerns they’re seeing at home.

Katherine:         

Alexandra, we received some questions from audience members prior to the program. Amelia wants to know, are bispecific antibodies covered by Medicare?

Alexandra:        

I believe they are. I would have to double-check, but I’m fairly certain some of our patients have Medicare and have had bispecific antibodies.

Katherine:     

Okay, so for the patient who is getting the bispecific antibody treatment, what are the lifestyle alterations that we as care partners need to make? Any changes to their diet?

Alexandra:        

No. I mean, a lot of patients definitely want to maximize anything they can do to make themselves feel better and help their myeloma respond. But what we’ve seen is that there’s not one particular diet or cutting out one particular food that’s going  to make a long-term or significant impact on any cancer therapy. The best thing that you can do in terms of diet or lifestyle is to try and just maintain a healthy lifestyle to balance all your other medical needs. You want to make sure your blood pressure is in good control.

You want to make sure if you have diabetes, that your blood glucose is in a good range. Because having those things be in good control is going to make your therapy and potential complications more manageable. 

Katherine:         

Okay. Can bispecific antibodies cause anemia?

Alexandra:        

Yes. So, bispecific antibodies, all of the three that are approved, can cause lower blood counts in all of your blood counts. Red cells, white cells, and platelets.

I will say we’ve usually seen that happen more at the beginning of therapy, and then as patients are on the therapy longer, their counts do tend to recover. So, whether that is from just the initial disease response, or it might be from the cytokine release syndrome, we see low blood counts with that, we don’t always 100 percent know. But it certainly can lower all of your blood counts.

Katherine:         

Okay. Gina asks, is there any home equipment we will need to help during treatment?

Alexandra:        

Nothing is required. So, you’re not required to have any sort of medical devices at home. Well, I’ll take it back. I would like everyone to have a thermometer so that if you do feel sick, you can at least check your temperature. Sometimes having a blood pressure cuff or an oxygen monitor at home, that can be helpful if you’re not feeling well, just to see if things are out of range. But there’s definitely not a requirement for those things at home.

Katherine:         

Okay. What can care partners do to help the patient have a more positive outlook during therapy, especially when they’re feeling down and depressed?

Alexandra:        

Sometimes I think the best thing that you can do is acknowledge that this is really hard. I mean, changing therapy, having myeloma, going through a hospital stay is really challenging. And sometimes patients just need to hear, “This is a really hard situation, and you’re doing a great job. Taking all your medication, going to the hospital for these treatments, coming to your follow-ups.” Even those small things, giving encouragement and acknowledging how hard that is, even if it seems like it’s not a big thing, can really give a patient a different perspective on how things are going.

Katherine:         

Are there support groups specifically for care partners?

Alexandra:        

We do have a care group, a support group here at Dana-Farber that is for care partners, run by our social work team. I think it is both now virtual and live, but I’m not positive if they’ve gone back to in-person support groups yet. But I do think the American Cancer Society has some good online groups as well.

Katherine:         

Okay, that’s good to know. Thank you. So, before we end the program, Alexandra, I’d like to get your thoughts about the topic. What message do you want to leave the audience with?

Alexandra:        

I would tell them that bispecific antibody therapies are a great option for patients in the current myeloma setting. I know that being in the hospital for a week is an incredibly big ask, especially after everything patients are going through with their treatments and then having their disease progress. But the inpatient stay for the long term, hopefully, outpatient benefit of a quick injection every other week with minimal toxicity is certainly worth it. And so I would try to keep an open mind about bispecifics and get excited about them.

Katherine:         

Thank you so much for joining us today, Alexandra. We really appreciate it.

Alexandra:        

Thank you so much for having me.

Katherine:         

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following the webinar.

It will help us as we plan programs in the future. To access tools to help you become a proactive care partner, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.

Elevate | What Role Can YOU Play in Your Myeloma Treatment and Care?

How can you elevate your overall myeloma care and treatment? Myeloma expert Dr. Sikander Ailawadhi discusses advances in myeloma care, the importance of patient participation in myeloma treatment decisions, and shares key advice and resources for self-advocacy.
 
Dr. Sikander Ailawadhi is a hematologist and oncologist specializing in myeloma at Mayo Clinic in Jacksonville, Florida. Learn more about Dr. Ailawadhi.

Related Resources:

Self-Advocacy in Myeloma Care | Advice From an Expert

Self-Advocacy in Myeloma Care | Advice From an Expert 

Myeloma Combination Therapy _ What Patients Should Know

Myeloma Combination Therapy | What Patients Should Know 

What Should You Know About Emerging Myeloma Treatment Options? 

Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell. It’s no secret that the quality of care that patients receive can vary depending on a number of factors and patients who are educated about their condition and involved in their care may have improved outcomes. That’s why the Patient Empowerment Network developed the Elevate Series, which aims to help patients and care partners be informed about their disease and more confident participating in conversations with their healthcare team.

In today’s program, we’re going to hear from an expert to learn more about myeloma and hear tips and advice for accessing better overall 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. Well, let’s meet our guest today. Joining us is Dr. Sikandar Ailawadhi. Dr. Ailawadhi, welcome. Would you please introduce yourself?

Dr. Ailawadhi:

Yes. Thanks a lot, Katherine. Thanks for this opportunity. To all our viewers, listeners, I’m Sikandar Ailawadhi. I’m one of the hematologists oncologists at Mayo Clinic in Jacksonville, Florida. So, at this Jacksonville, Florida site of Mayo, I lead our myeloma group, and we have a very comprehensive program with inpatient outpatient treatment and lots of clinical trials, cell therapy, et cetera. I look forward to the discussion.  

Katherine:

Well, thank you so much for joining us today. I know you’re a busy man. I’d like to start by discussing your role as a researcher. You’re on the front lines of advancements in the myeloma field. So, what led you here, and why is it so important to you?   

Dr. Ailawadhi:

Yeah. So, Katherine, thanks for asking that question because before jumping into the disease state and clinical trials and data, et cetera, I think it’s important for all of us to keep in mind what kind of brought us here or what kind of keeps driving us further. So, I think for me, the decision to come to the field of multiple myeloma was very strongly influenced by my mentors.

My mentor who shaped my career and also got me interested in this area. I think during my training, it was the time that newer drugs were just beginning to come about. So, the field of myeloma was just beginning to change. And since then, obviously, there have been lots of advancements, lots of research, clinical trials, new drugs, so that the outlook for not only the myeloma patients has improved quite a bit.   

But also, for physicians, researchers, us academicians who work in this field, the opportunities are much, much more. And because I trained at a large academic center, I – and again, with working with my mentor, I got so interested in the clinical research because frankly giving the available drugs is one thing but being at that cutting edge where you can bring newer drugs to life, newer drugs to our patients’ lives, that was what was most important for me and is the driving force for my work today.  

Katherine:

Thank you for that explanation, Dr. Ailawadhi. I appreciate it. So, when it comes to choosing therapy for myeloma, it’s important to work with your healthcare team to identify what might be best for you. How would you define shared decision-making and why is this so critical to properly managing life with myeloma?  

Dr. Ailawadhi:

Excellent question, Katherine. Shared decision-making or a process in which the physician, the health care team, and the patient, their caregivers, everybody comes together, shared, to make a decision that we feel is in the best interest for that patient at that time. That is the whole concept.  

Whenever we think about treatment decisions, in our mind, the three main components that have to be considered every single time. Not just newly diagnosed or relapsed or third line or whatever, every single time a treatment decision has been taken, we must consider patient-related factors. What is their preference? What are their goals? Do they have caregiver support? How far do they live? Do they want IV? Pills? Any side effects that are there?  

Comorbidities? Other issues? Financial conditions? Everything comes into play, patient-related factors. Then, there are disease-related factors. How fast is the disease growing? Is this new? Is this old disease, high-risk, low-risk, or standard risk? Or what has been given before, et cetera. So, patient and disease-related. And the number three is the treatment-related factors. What is being considered for the patient? What are the ins and outs, pros, and cons?   

All of this has to be laid out in front of the patient and preferably also their caregiver if the patient has someone who they can share their decision with.  

And when we put all of that in the mix, we come up with a decision which is hopefully in the patient’s best interest. They are more likely to go through with it. They are informed. They are involved in their care. And then, hopefully, if the patient starts on a treatment that they are interested in, knowledgeable about, and committed to, we’ll be able to keep the patient on that longer term and get the best benefit out of it.   

So, in my mind, the main reason for shared decision-making is to make sure my patient is committed to that treatment. They understand that treatment. And we make this kind of bond between us as clinicians and our teams and the patient and their home team, their family team, their caregiver team so that everybody is working together with a singular goal. Right treatment for the right patient at the right time because it must be patient-centric, not research or clinician, or drug-centric. 

Katherine:

Yeah. Okay. That’s good advice. What are myeloma treatment goals, and how are they determined?   

Dr. Ailawadhi:

So, I think the myeloma treatment goals can be very different depending on what vantage points you’re looking from. My treatment goal is to provide the best treatment for my patient that has least side effects, gets a deep control, and my patient’s able to live long with a good quality of life. Okay. But that’s my goal.  I need to figure out what my patient’s goals are, and sometimes our patient’s goals are very different. A patient’s goal might be that they want to really avoid side effects. Well, they want to live, lead their quality of life, and keep traveling. And this happens on a day-to-day basis.  

Just the other day, one of the patients said, “Well, I really want to keep driving around in my RV with my wife, because that is what we had wanted to do at this point of our life. What can you do to help me control my disease, but keep me driving my RV?” And we literally had to figure out where all they were traveling. We identified clinics close to them and connected with physicians so that they could continue their treatment wherever they were. So, the patient’s goals are very important, and in fact, I would say they are paramount. So, understanding what the patient wants. They may be wanting to control pain. They may be wanting to just live longer.  

They may be wanting to delay treatment so that they could watch their daughter’s soccer game. I’m just saying that the goals can be very different. It is important to lay them out. Every time you’re making a treatment decision, the goals should be laid out into short-, mid-, and long-term goals. I should bring my goals to the discussion. The patient should bring their goals to the discussion, and we come up with whatever is the best answer for them that suits them.  

Katherine:

So, you’re trying to maintain an open dialogue, an open line of communication, yeah.  

Dr. Ailawadhi:

Absolutely.  

Katherine:

What sort of tests should be done following a myeloma diagnosis?   

Dr. Ailawadhi:

Generally, when myeloma is suspected, we need to know what the basic blood counts are, something that is called a CBC, complete blood count. We’re looking for anemia, low white blood cells, low clotting cells, or platelets. We want to do serum chemistries or blood chemistries, looking for kidney function, liver function, electrolytes, calcium, et cetera.   

Then, we want to do some kind of an imaging of the body. Generally, routine X-rays are no longer done, and the most preferred is a PET-CT scan, a PET scan. We do PET-MRIs frequently. So, there are different tests available, but you want a good test to know what’s the state of bones and presence of any lesions or tumors. And then, the important question comes is doing a bone marrow biopsy.   

The reason for doing a bone marrow biopsy, and even if somebody has had a biopsy done from a compression fracture, et cetera, that diagnosed myeloma, a bone marrow biopsy still should be done. It gives us a lot of pieces of information.  

It tells us what is the percentage of plasma cells in the bone marrow. So, what is the disease burden we are starting with? Secondly, that bone marrow biopsy specimen can be sent for what is called a FISH testing, which is fluorescent in situ hybridization.  

It is basically looking for any mutations in the cancer cells. Based on those mutations, myeloma can be classified into standard or high-risk myeloma. And sometimes our treatment choices are differed based on whether somebody is standard or high-risk. So, blood work, basic counts – and I skipped over one of the things. Right after chemistries, I wanted to add also are myeloma markers.  

There are typically three lab tests of myeloma markers. One is called protein electrophoresis. It can be run in blood and urine. Ideally, it should be run in both. One is immunoglobulin levels, which gives us the level of IgG, IgA, IgM, et cetera. And the third one is serum-free light chains, which is kappa and lambda light chains. Neither one – none of these tests eliminates the needs for the other.

So, everybody, in the beginning, should have complete blood count, blood chemistries, SPEP or serum protein electrophoresis, urine electrophoresis, immunoglobulins, light chains, imaging, and then a bone marrow. This completes the workup. Then, based on that, the treatment can be determined.  

Katherine:

Well, you mentioned lab work. How often should tests and blood work be done?   

Dr. Ailawadhi:

Good question. Very, very important question because we see very frequently that the patients come in, they’re getting treatment somewhere, and every single time the patient steps foot in the door of that institution or wherever they’re going, they got a blood draw. That’s how they start their day. It’s needed more frequently in the beginning but needed less frequently later on.

Generally, the myeloma markers, those protein electrophoresis, immunoglobulins, light chains, they are frequently done just about every month. Generally, in myeloma, one month, three to four weeks is one cycle. So, at the beginning of every cycle, you want to know how good your response was. So, the myeloma markers once a month.  

The blood counts and chemistries in the first month, first one to two months, they can be done every other week or so just to make sure counts are fine, no need for transfusions, kidney/liver is okay, et cetera. But after the first couple of months, when the body is used to the drugs when the patient is settled with the treatment, frankly, once-a-month labs are good enough. We don’t really need labs on every single treatment visit. Because the other thing that happens is some of these drugs can lower the blood counts normally during treatment, but they have a rest period at the end of the cycle when the counts recover.

So, if somebody does labs in the middle of the cycle when the counts are expected to be down but not an issue, treatments are stopped, and growth factors are given. And this is done, but that is not really necessary. So, first couple of one to two cycles, maybe every other week to make sure counts are okay. Myeloma markers monthly, but after the first couple of months when things are settled, once a month should be sufficient.   

Katherine:

Okay. What questions should patients be asking about their test results?   

Dr. Ailawadhi:

Yeah. Very, very, very important. In fact, whenever I’m speaking in a patient caregiver symposium or anything, I spend a lot of time on these test results because frankly, a lot of times it sounds like jargon and the people talk about, “Oh, my ratio is going up,” or the doctor is saying, “Hey, your immunoglobulins are normal. You’re in remission.” But so, I think the patients need to understand and ask from their doctors, “What is my marker of the disease that you will be following?” And I’ll tell you that immunoglobulins, that IgG or IgA level, is nearly never the marker. It’s either M spike or light chains, generally one of those.  

So, the patients need to understand what is their marker. They also need to know what did their bone marrow show. What was the percentage and what was the FISH result or cytogenetic result? I think other than the tests, I will also add the patients need to ask their doctor a lot of these questions that you’re asking me. How frequently are the labs going to be done? Why is it important? Why was a certain treatment selected? What is the expected outcome? What are the chances that I can go into remission? How long does the intense treatment stay?  

When does it go to some kind of a maintenance? Et cetera, et cetera. Basically, you want to understand everything about the disease and its treatment. It is overwhelming. This is a lot of information. A lot of times the patients may say, “Well, I got a diagnosis. I got a treatment started. I just need to move on.”  That’s right. But once you spend all that time initially understanding your diagnosis and the treatment and the disease, it’ll make the rest of the journey much, much easier.  

Katherine:

That’s really helpful as we drill down a little further. What are the types of treatments available for people with myeloma?   

Dr. Ailawadhi:

So, myeloma has a lot of treatments available. We can classify these treatments into different classes of drugs, or we can classify the treatment as early lines or late lines of therapy. Or we can classify these treatments into cellular therapy or targeted therapy or chemotherapy. There are ways of classifying it.  What I would suggest is we should think about classes of drugs. We have something called proteasome inhibitors. That class has three drugs FDA-approved. We have something called immunomodulatory drugs. That class has three drugs also approved, but generally, we use two.   

Then, there are something called monoclonal antibodies. There are three drugs approved there as well.   

There are cellular therapies or CAR T-cell therapy. There are two of them approved. There is also a stem cell transplant that is used as a part of treatment sometimes but is different from CAR T. Then, there are other immunotherapy, something called T-cell engagers, in which also there are three drugs approved. In fact, as I’m saying to you, I’m trying to think…yeah, wow. Every class has three drugs. That’s so weird. And then, there are some other classes of drugs. There is something called exporting inhibitors. There is a drug there. All said and done, there are these different classes of drugs.  

There are some guiding principles for myeloma treatment. Generally, three to four drug combinations or regimens are better than two drugs. So, a patient should be in the initial therapy or later lines. Also, preferably be getting a three-drug combo. And I forgot to mention steroids, which are an important part of every regimen in myeloma, almost every regimen. So, three drugs or four drugs are better than two. That’s important to keep in mind. Longer durations of treatment are generally considered better. We should not tinker with the regimen’s recipe too soon. As long as the patient is tolerating for a longer duration before making any major changes like maintenance.    

Generally, maintenance in myeloma is not a response-assessed thing like, “Oh, you’ve responded in two months. We should go to maintenance.” Generally, in myeloma, maintenance transition is a time-dependent thing. Okay, you’ve had six or nine months or 12 months. We can go to maintenance, sort of a thing. So, even if somebody has responded, they may need the same treatment for a longer period of time to keep the disease quiet.  

And so, I think these are the different categories of drugs. We pick and choose from different categories to combine and make a regimen. The CAR T-cell therapy, the two CAR Ts that are approved, or the three T-cell engagers that are approved, they are all currently used as single agents. They are not combined with anything, not even with steroids. 

Katherine:

Yeah, I see. How do clinical trials fit into a treatment plan?   

Dr. Ailawadhi:

Okay, that’s an extremely important question, and you’re asking it from a person in my clinic about two-thirds of the patients who are on treatment at any given time are on clinical trials. So, I am very heavily, I shouldn’t say biased, but a proponent of clinical trials. In my opinion, clinical trials are a part and parcel of treatment for every single patient. In fact, when you look at the NCCN guidelines, which are National Comprehensive Cancer Network, which is large institutions across the country, and they make guidelines for all cancers, it is mentioned in every single setting that clinical trials should always be considered.  

So, I personally feel that whenever the patient is coming up with a treatment decision, we talked about shared decision-making in the beginning, it’s important for them to ask at every single juncture, “Do you have any clinical trials available for me? 

And if you don’t have any clinical trials available, are there any clinical trials that I should consider, even if it means going to a different place and getting an opinion?” I know logistically it’s challenging, but we should at least know our options. So, in my opinion, clinical trials should be considered at every single juncture, because that is how patients get access to either a new drug, a new treatment, or a different way of using the current drugs, which might actually improve upon their current state. So, everybody all the time should consider clinical trials.   

Katherine:

That’s great information, Dr. Ailawadhi. Thank you for that. I’d like to add that if you’re interested in learning more about emerging treatments, such as CAR T-cell therapy, PEN has a number of resources available for you, and you can find these at powerfulpatients.org/myeloma, or by scanning the QR code on your screen.   

So, the symptoms of myeloma, as well as the side effects of certain medications, can vary greatly among those being treated. How do you approach symptom management with your patients?   

Dr. Ailawadhi:

It is extremely important that we focus on the symptoms, whether it’s coming from the disease or it’s coming from the treatment. Because frankly, if a person is responding to the treatment, you want them to stay on the treatment for a longer duration of time, so the disease can stay controlled. 

If we don’t handle the symptoms from the treatment or the side effects that are happening or if the disease is causing too many symptoms, it is more likely that either we’ll start cutting down the drug too much or stopping the treatment, et cetera, and then the disease just comes back. In some cases, that is necessary, but generally we would like to modulate the treatment or address the symptoms.  

So, one important piece that we should do, or at least we try to do over here, is that every single time that we talk to the patient for any of the visits – while there is enough time spent on, “Well, these are your labs, your diseases responding markers, SPEP, and M spike, and light chain,” and all that stuff – we spend a lot of time asking about symptoms.  

It is, I understand, challenging to cover everything, but to familiarize what drugs cause what kind of symptoms, and at least making sure that we ask those from the patient. For example, IMiDs like lenalidomide (Revlimid) can cause some diarrhea, can cause fatigue, can cause sleepiness. Well, I must ask about diarrhea from all my lenalidomide patients.  

Bortezomib (Velcade) can cause neuropathy. It can give rise to shingles. I must ask my patients for every bortezomib-treated patient. “Hey, do you have any neuropathy numbness, or tingling?  

Are you taking your medication to prevent shingles, et cetera?” I’m just saying we may not be able to do a comprehensive review of every single symptom from every single patient, but whatever the target side effects are important to know every single time. We educate the patients about these side effects so that they are aware of them, and they can report these side effects. And then, if the side effects are happening, any symptoms are happening, then is it to the point that we need to stop the treatment?  

Frequently, we do take drug holidays for a few weeks just to make sure, okay, we know is it coming from the drug or the disease? And every now and then, we realize, well, the drug was not even causing the symptom, because we stopped it, and the symptom stayed. Or so then, why stop the drug? There’s no point stopping it if I can’t control the symptom. So, understanding whether it’s coming from disease or drug or something else, addressing them, making the changes appropriately to lower the dose, space them out, et cetera. All of that is done. And of course, like I said, importantly, educating the patient is so very important. I’ll add one quick thing. We focus on the drug-related effects.  

As you rightly mentioned, Katherine, the disease itself can cause a lot of symptoms. So, generally, when I see a new myeloma patient, in the first couple of visits, we’ve done all the testing, we’ve discussed the treatment, and we’ve addressed some of the basic symptoms like pain, for example. That is big in myeloma.

But then, when the patient has started treatment, generally within the first two months, the focus that our clinic has is we need to control any side effects, and we need to address any symptoms that are being left over from the disease. And that’s when we start referring patients to interventional radiology for any bone procedures or palliative care for pain control or neurology for neuropathy, whatever so that we are controlling all the symptoms.  

And that’s when we hopefully get the patient as close to their baseline as possible.   

Katherine:

I would like to talk more about self-advocacy, Dr. Ailawadhi, managing the worry associated with a diagnosis, concerns about relapse, side effects. It can lead to emotional symptoms like anxiety and fear for many. So, why is it important for patients to share any worries they’re having with their healthcare team?   

Dr. Ailawadhi:

Yes. Extremely important. See, nobody’s thinking, “Okay, I’m going to have cancer today.” Nobody’s prepared for it ever. Cancer is always a diagnosis that comes out of the blue, blindsides us, and then suddenly we have to change the rest of our life because of it.  Not only our life, our caregiver’s life, family’s life, everything changes.  

So, it is okay to admit that it is difficult. It is okay to admit that we need help. And, Katherine, I like your kind of the use of the word, self-advocacy, although I want to qualify it.  

A lot of times we say patients got to be their own advocates. But if a patient doesn’t know what to ask, they’re going to be lost. My thought is it is okay to – the first and foremost that a patient or their caregiver can do is please report your symptoms or how you’re feeling. And those symptoms could be physical, those could be psychological. 

Please report what are you feeling, what are the symptoms. On a drug, what are the side effects, et cetera, so that your healthcare team can try to address them. Don’t ever assume, “I am on chemotherapy. I should have diarrhea.” No. Don’t think, “I’m on chemotherapy. Other patients outside in the waiting room look sicker than I. I feel embarrassed to ask a question.”  

We hear this so many times. A lot of patients will say, “I feel embarrassed to ask that I’m going through this symptom, because I see sicker people outside.” Yeah, but know when I’m with you as a patient, you are it. I’m not thinking about anybody else. And I don’t want anybody else’s decision to obscure or cloud our relationship at that visit. Please report your symptoms. Please ask for help.  To me, that is good enough self-advocacy. Self-advocacy is not saying, “I should get this treatment, not that treatment.” But self-advocacy could mean, are there clinical trial options?  I know I live far away from a large center. Could I get a tele-visit with a large center? Could I get a second opinion from someone? Those are all very, very reasonable questions, and by asking those questions, a patient is advocating for themselves.  

Katherine:

As you alluded, there’s a whole healthcare team working with each patient, and there’ll be people on that team who can help support a patient’s emotional needs. So, one thing that’s on the mind of many viewers is the financial aspect of care. And you mentioned that earlier everyone’s situation is different, of course, but where can patients turn if they need resources for financial support

Dr. Ailawadhi:

Very important question. I can tell you every day when I come into my office, my nurse has a stack of documents ready for my signature. Every single day. Today, there was only one, but there could be different numbers. And these are generally from foundations from diagnosis confirmations, et cetera. Things that we are filling on and signing on behalf of our patients so that they are able to receive resources, whether it’s from a pharmaceutical manufacturer, a foundation, or society that has funding available, et cetera. I should start by saying, Katherine – and I feel embarrassed to admit this, but I should start by saying, I may not have all the answers for my patient during that visit.   

But I think the very important piece where we can start is asking the patient, “Is this causing any financial strain on you?” As I mentioned earlier, we don’t think about, “Oh, I’m going to have cancer today. Let me prepare for that.” Or “I’m going to have cancer five years down the road. Let me prepare for that.” We’re not always ready for this. It’s okay. It’s important for me to ask if there is a problem, and it’s important for the patient to admit there’s a problem or say, “Well, I’m having difficulty with copayments.” And whatever may be difficult for one may be okay for the other. So, I shouldn’t assume. So, that discussion must happen.

Generally, in our setup, what happens is if the patient brings up a concern, if I identify a concern, or if we think something may be going on, but we’re not very sure about it, we tend to bring in our social workers. The social workers are typically the ones who are able to do that discussion with the patient, talk about what are the resources available. What are the foundations that we can apply to? We have patient navigators who can do the similar things. So, the patient navigator, social worker, there are different individuals who will be able to provide much more granular information. I also strongly suggest patients to join support groups.

There are lots of resources, which I may not be aware of during our visit with a patient, but I can connect to the social worker, their patient navigators, and online support. 

Katherine:

Thank you for that. It’s great advice. As we close the program, what would you like to leave the audience with? Why are you hopeful?   

Dr. Ailawadhi:

First of all, I should admit, yes, I’m very, very hopeful for myeloma. I started my work with myeloma or my time working in this field in somewhere around the year 2000 or around that year. In the early 2000s, the average survival of a myeloma patient despite treatment was about two to three years.

Today, while national data is suggesting somewhere in the vicinity of 10ish years, give or take, all of us who are myeloma-focused physicians and have specialized centers that we work in, we have many patients who are living in excess of 10 years and pushing the envelope. In fact, my longest survivor is now maybe 34, 35 years with myeloma, and she’s not even been on treatment for a few years.  

This is what gives me hope. That it’s not only that patients are living longer, more and more patients are living with less disease burden, better quality of life, and in a lot of cases, not even on a treatment. Our myeloma world is now going from everybody should be treated forever and ever to there are many a clinical trial that are testing the hypothesis of, “Can we stop treatment? Who needs to be treated? Could we be getting closer to that elusive cure that we all are looking for in myeloma?”

So, to me, the hope is newer drugs that are better tolerated, providing better quality of life for patients. And in a lot of cases, the patients are not even on treatment. That is where we think we are making a change and making a difference. And you had started by asking me, “What is the driving force?” That to me is the driving force of why we get excited to come to work every morning, because we know that we can help someone else, and we can learn something new.

Katherine:

That’s very promising, Dr. Ailawadhi. Thanks so much for taking the time to join us today.  

Dr. Ailawadhi:

Absolutely. Thanks a lot for this opportunity.   

Katherine:

And thank you to all of our collaborators. 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 being with us today.

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy from Patient Empowerment Network on Vimeo.

What are bispecific antibodies, and how are they advancing myeloma care? Dr. Omar Nadeem of Dana-Farber Cancer Institute discusses the role of this new therapy in myeloma care, shares an update on ongoing bispecific antibody research, and compares this treatment to CAR T-cell therapy.

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.

Download Resource Guide

See More from Evolve Myeloma

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What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

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Myeloma Research Highlights From ASH 2023 

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What Should Myeloma Patients Ask About Developing Research?

Transcript:

Katherine:

Well, another therapy that has emerged in myeloma is bispecific antibodies. What patient type is this therapy right for? 

Dr. Nadeem:

So, bispecific antibodies are great because they’re off the shelf. What that means is that CAR-T cells, we first have to collect the T cells and we then have to send them off to be manufactured, and that manufacturing process can take up to a month, sometimes even longer, for some of the current available CAR-T products.   

And then, after the cells are returned to the facility, we then give usually three days of chemotherapy to try to suppress some of the immune systems of the patients. So, that way, when the cells are administered, they can expand robustly and do essentially what they need to do. 

So, that whole logistical process can take a couple of months by the time you identify somebody for CAR-T cells and then, from that moment until they can actually be treated. With bispecific antibodies, if we think somebody’s ready to go, you can basically get it as soon as we can have somebody ready to go either in our clinic or on the in-patient facility.

So, they’re much easier. They also utilize T cells to attack myeloma cells. We now have three approved bispecific antibodies. Two of them are targeting BCMA, the same exact target that we have in CAR-T cells, and one of them is now targeting a new target called GPRC5D, which is also highly expressed on myeloma cells.  

So, having all these bispecific antibodies available is excellent because patients can have access to them a lot faster and now we’re trying to answer the question of sequencing. Can you give bispecific antibodies after CAR-T cells for example? Can you give one bispecific antibody after another, especially if there’s a different target that we now have available?  

As a whole, though, bispecific antibodies tend to have lower response rates than CAR-T cells, particularly cilta-cel (Carvykti), which is cilta-cel that has a very high response rate of close to 100 percent.  

Most bispecific antibodies have response rates somewhere around 70 or so percent, so about two-thirds of patients respond to these therapies, again, in that fifth line or four or more lines of therapy. So, in that space, that’s the response rate. And across the board, generally speaking, patients benefit from these bispecific antibodies approximately a year on average. Some of the studies have shown longer benefit, and it also depends somewhat on response to therapy.  

Patients that have a really deep response can go even way longer than that. So, it is quite mixed in terms of how somebody may do on these bispecific antibodies, but those are the numbers.  

Katherine:

Well, it sounds like bispecific antibodies have really transformed myeloma treatment options.  

Dr. Nadeem:

Absolutely, and what goes hand in hand in this.  

I mentioned the logistics of CAR T, but then there’s also the supply and availability of CAR-T cells. Since the approval, the demand for CAR-T cells has been very high because of all these excellent results, but the supply really hasn’t been there. So, even at a center as busy as ours, we can only treat a handful of patients with CAR T-cell therapies compared to bispecific antibodies, where that is essentially an injection similar to many other approved myeloma agents that you can just readily treat patients with. So, CAR-T cells, while I think, again, have higher efficacy, with that comes slightly higher toxicity as well. It’s a very different kind of treatment program.  

And then, patients get a treatment-free interval, which you don’t see yet with bispecific antibodies. On the other hand, bispecific antibodies are readily available, slightly lower response rates, slightly lower toxicity when it comes to at least the traditional T-cell directing toxicities. And then you have, again, the readily available nature of it, which I think is hugely beneficial for patients.  

Katherine:

You talked about some specifics regarding bispecific antibodies, but are there updates in bispecific antibody research that you’d like to share? 

Dr. Nadeem:

Yeah, so, again, kind of following the theme of what we just said about CAR-T cells, can you bring these antibody therapies earlier? And there’s ongoing trials now looking at it in newly diagnosed multiple myeloma and early relapses, and then we presented our data at ASH this previous year looking at it in high-risk smoldering myeloma. We treated patients with teclistimab (Tecvayli), which is a BCMA bispecific antibody that is approved for relapse refractory patients. And what we demonstrated in that study is that people that got teclistimab had a 100 percent response rate with an MRD-negative rate. So, kind of as deep of a response as we can measure, also at 100 percent.  

So, this is something that we had not seen before. When their immune systems are a lot healthier, they may benefit more. So, hopefully we’ll see confirmation of these results in other trials.  

Particularly in the newly diagnosed space because we do think that these antibody therapies have such huge potential to treat patients, and then hopefully we’ll have durable responses. So, I do think that some of this paradigm may shift over the next few years, and then there’s also combinations that are currently being studied: combinations with traditional myeloma therapies, such as monoclonal antibodies, other immunomodulatory agents, or proteasome inhibitors. All these combination trials are now ongoing to see can you improve upon some of those numbers that I highlighted before with single-agent bispecific antibody therapy. 

Katherine:

Can you share the pros and cons of bispecifics and how it compares to CAR T?” 

Dr. Nadeem:

Yeah. I think we mentioned earlier that as a whole, they’re very similar. They’re both T-cell re-directing therapies, in many circumstances, with the same exact target of the myeloma cell, but because this isn’t a cell infusion – this is a cell injection – that you receive that redirects your T cells to the myeloma cells, you tend to see a little bit of a lower toxicity signal when it comes to the cytokine release syndrome incidents and severity. You see lower neurological toxicity, usually, than you do with CAR  T-cell products as a whole.  

With that comes slightly lower efficacy than you see with at least some of our CAR-T products, but if you respond to therapy, then the durability of response can be as good as you can achieve with CAR-T cells. One thing to note about the bispecifics, though, is that it is continuous therapy, so you are getting it on some regular schedule. Right now the approval is for it to be given weekly and then go to every two weeks after six months of therapy if you’re basically in a good response.   

A lot of that is to try to mitigate the risk of infection. So, that is one of the biggest things that we have seen with bispecifics more so than CAR-T cells. Because it is continuous administration of these therapies, that really suppresses your immune system significantly, and infection rates are quite high. So, we typically give other ways to try to mitigate that using immunoglobulin infusions to try to boost up your immune system. Typically, we do that once a month for patients, making sure you’re on the right prophylactic medications and then really adjusting the therapy and the schedule to you depending on your tolerability.  

So, as we said before, it’s an excellent option. I think bispecific antibodies are going to be the mainstay of myeloma therapy going forward because CAR-T cells, again, we can’t really treat everybody with CAR-T cells just simply because of the dynamics of how the process is. So, having the bispecific antibodies available for patients is excellent.   

Evolving Myeloma Treatment Options | CAR T-Cell Therapy

Evolving Myeloma Treatment Options | CAR T-Cell Therapy from Patient Empowerment Network on Vimeo.

What is CAR T-cell therapy, and who is it right for? Dr. Omar Nadeem of Dana-Farber Cancer Institute discusses the role of this therapy in myeloma care and shares an update in ongoing CAR T-cell therapy clinical trial research.

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.

Download Resource Guide

See More from Evolve Myeloma

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What Should Myeloma Patients Ask About Developing Research?

Transcript:

Katherine:

Well, I’d like to talk about some new and emerging therapies in myeloma, starting with CAR T-cell therapy. Can you talk about who this treatment option might be appropriate for?  

Dr. Nadeem:

So, yeah, just to kind of give folks background, CAR T-cell therapy is a form of immunotherapy, where we take out an individual’s T-cells and then re-program them, essentially, to recognize myeloma cells. Right now there’s two approved CAR-T products for multiple myeloma, both in the relapse refractory setting. It’s really for patients that have had four or more lines of therapy.  

So, that’s a lot of different combinations that we currently have available. Those therapies stop working before patients are actually eligible for CAR-T cells at the moment. Both of these CAR T-cell products have been gamechangers in terms of improving prognosis for patients.  

The good thing about CAR-T cells is that it is a one-and-done treatment. So, patients, when they go through that initial phase of therapy, they are then off therapy, although we are now starting to study certain therapies that we may administer after CAR-T cells to get them to last even longer than they currently do, but that’s still in, for example, that’s one of the clinical trials or many of the clinical trials that are currently ongoing now, to try to answer that question.  

So, a lot of patients can be eligible for CAR-T cells. They have to have the prerequisite amount of therapies. Again, there are some sort of baseline fitness characteristics that we look at for patient’s ability to tolerate it. But as a whole, I consider CAR T-cell therapy more broadly applicable to myeloma patients than compared to, let’s say, a stem cell transplant.  

Katherine:

How has this therapy revolutionized myeloma care? 

Dr. Nadeem:

Yeah, before the first approval, now a few years ago, in this space we didn’t really have anything like this to offer patients. So, many of the combinations and other compounds that were in clinical trials would have a response rate somewhere around, let’s say, 30 percent. So, 30 percent of patients may respond to that therapy in that space, and that may only last a few months, and that was considered successful not that long ago. Now, with CAR T-cell therapy and bispecific antibodies, these therapies are highly efficacious.  

You see response rates of 70 to 100 percent in some of these immunotherapies, and what that’s translating into is patient’s disease staying away for a year or two years, even three years in some of these clinical trials. And again, this is completely unprecedented compared to what we had before.  

Katherine:

I understand that there are a number of clinical trials for different types of CAR T, or even using it earlier in the disease. Can you share updates in CAR T-cell therapy research? 

Dr. Nadeem:

Yeah, so, exactly as you pointed out, there have been trials already, actually, that have been completed, Phase III studies looking at CAR T-cell therapies in earlier relapses.  So, patients that have had either one of two lines of therapy. 

Both our CAR-T therapies have been compared to standard of care in that space and have shown superiority, and this is something that we all have been kind of waiting for to see if you deploy it earlier, perhaps you’re going to see even greater benefit, and that seems to be the case in some of these trials, and now we’re awaiting, hopefully, approval of some of these CAR T-cell therapies to be administered earlier because in fifth line, it’s very different than treating patients in second or third line, which I think will really vastly improve our ability to deliver this therapy to many patients, as it can be quite challenging for patients that are in fifth line, to allow them to go through the process of CAR-T cells and then having them be administered.  

I was looking at it head-to-head with stem cell transplant, as I mentioned before, and this is in the context of quadruplet and induction therapy followed by either CAR-T cells or stem cell transplant, and then followed by maintenance therapy. So, really trying to see if I can overcome what we typically have achieved with stem cell transplantation.  

We also are doing some studies even before that. So, patients, again, in high-risk smoldering myeloma, which we know have an increased risk of developing newly diagnosed disease in the next few years, perhaps that could be the time where we can give some of these immunotherapies, and that’s some work that we have going on at our center. 

Evolving Myeloma Treatment Options: How You Can Access Cutting-Edge Care

Evolving Myeloma Treatment Options: How You Can Access Cutting-Edge Care from Patient Empowerment Network on Vimeo.

With the quickly evolving landscape of myeloma treatment and care, it’s important to work with your healthcare team to determine a care plan. In this program, Dr. Omar Nadeem discusses the latest updates in research and clinical trials, the role of new and emerging therapies– including bispecific antibodies and CAR T-cell therapy–and shares advice for accessing quality 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.

Download Resource Guide

See More from Evolve Myeloma

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What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

Questions to Ask Your Doctor About CAR T-Cell Therapy

Questions to Ask Your Doctor About CAR T-Cell Therapy

Considering CAR T-Cell Therapy for Myeloma_ Key Questions to Ask Your Doctor

Considering CAR T-Cell Therapy for Myeloma? Key Questions to Ask Your Doctor 

Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. As patients collaborate on treatment decisions with their healthcare team, it’s important that they understand all of their options and how these options may be impacted by research developments. That’s why the Patient Empowerment Network created the Evolve series, to arm you with the latest information and help you feel empowered and confident during conversations about your myeloma care.  

In today’s program, we’re going to hear from an expert in the field about the evolving treatment landscape and discuss how you can play an active role in your 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 may be best for you. Well, let’s meet our guest today. Joining us is Dr. Omar Nadeem. Dr. Nadeem, welcome. Would you please introduce yourself.  

Dr. Nadeem:

Thank you. Hi, everyone. My name is Omar Nadeem from the Dana-Farber Cancer Institute. It’s my pleasure to be here.  

Katherine:

Thank you so much for joining us today. Before we get into our discussion, would you share with the audience how the field of myeloma care has changed over the course of your career?   

Dr. Nadeem:

Yeah, and things are changing so rapidly. My career started after my training in 2015 and at that time, daratumumab (Darzalex) just had its approval in relapsed/refractory multiple myeloma. That, along with several other monoclonal antibodies a few immunomodulatory drugs and proteasome inhibitors.  

At that time, it felt like myeloma was at the forefront of significant advances and change in practice, which it was. Little did we know that we were right around the corner with the next renaissance of myeloma therapy, which is these immunotherapies that have been approved over the last three to four years now. So, safe to say things are changing so, so fast and it’s leading to excellent outcomes for patients.  

Katherine:

Yeah, it’s great news. So positive. I’d like to start with the importance of a patient’s healthcare team. What are the benefits to seeking care with a myeloma specialist, even if it’s just for a second opinion or a consult? 

Dr. Nadeem:

Yeah, so, myeloma is a little less than 2 percent of all cancers, and it’s the second most common blood cancer, so certainly not rare. With that being said, if you go to a general community practice, they don’t typically see too, too many patients with this disease. So, alongside that, we have so many different treatment options and combinations and these, as I mentioned, immune therapies.  

And other therapies that are only actually carried out at academic centers for now, such as stem cell transplants, and CAR T-cell therapy. I think it’s important to kind of meet with an academic provider just to get a sense of what the patient may be facing, both in that immediate time, but also in the future, because a lot of myeloma therapy is lifelong. And in that case, you do have to come up with a plan for your whole treatment in a way early. So, it’s important to kind of one: hear it from another person, and then two: really sort of figure out what the outlook would look like for the individual patient.  

With that being said, many of our myeloma regimens that are approved can very easily be given at the local provider, and that’s usually our preference, for patients to be treated closer to home. So, ultimately, this is another way for patients to get input about their treatment program, but also talk about the future.   

Katherine:

That makes sense. Specialists at academic medical centers are typically more involved in research and clinical trials. 

And patient participation is essential to advancing medicine. So, how do clinical trials impact myeloma care? 

Dr. Nadeem:

Well, everything that we have available today for myeloma therapy was once in a clinical trial. So, all these promising therapies usually start in early phase studies and move on to Phase II and Phase III studies, and then those are the ones that the FDA uses to approve a particular combination.  

So, it all depends on kind of where someone is in their disease course. It also kind of depends on what their preferences may be in terms of taking on something that is beyond standard of care. So, as part of any clinical trial in whatever phase it may be, whether its newly diagnosed multiple myeloma, even smoldering myeloma, which is one step before that, relapsed/refractory myeloma.

At each step of the way, there are clinical trials that are there trying to improve upon what’s already out here, right? So, we are, despite all these amazing advances, unfortunately, the disease is still not curable for a vast majority of patients.  

In that case, how do we move to that cure, or how do we kind of advance the disease even beyond this? And a clinical trial is a way to do that.  

Katherine:

What type of patient is most appropriate for a clinical trial? 

Dr. Nadeem:

So, there are criteria that each clinical trial uses in terms of eligibility. Some of that has to do with the disease characteristic itself, kind of where somebody is in their disease course, but many times it’s also patients’ fitness, organ status in terms of kidney function, their blood count to some extent, heart function, etcetera. There are some sort of minimal prerequisite guidelines that we have to enroll patients in trials. So, it really, again, depends on where somebody is in their disease course and what they may be willing to take on beyond what may be offered to them as part of standard of care.  

Katherine:

What questions should patients be asking if they’re entrusted in participating in a clinical trial? 

Dr. Nadeem:

I think the important thing is to sort of first recognize what’s available to them as part of standard of care and then what the clinical trial is trying to answer.  

So, for example, if it’s newly diagnosed multiple myeloma, we now have quadruplet regimens that we give to patients at the time of their diagnosis, and then the next natural question for eligible patients that now comes up is whether they should do a stem cell transplant or not.  

And alongside that goes with all these advances in immune therapies, such as CAR T-cell therapies and bispecific antibodies. And there are now trials looking at those therapies and comparing them, for example, to stem cell transplant to try to answer the question “Can we get even beyond something like a stem cell transplant?” 

So, that’s one example of a trial where a patient may be interested in saying “Okay, well, a transplant may be my standard path, but what if I try to enroll in this study and get randomized, for example, to the CAR-T arm? Then, perhaps, I’m getting access to some of these therapies early and maybe that’s going to improve my outcomes.” 

Katherine:

Well, I’d like to talk about some new and emerging therapies in myeloma, starting with CAR T-cell therapy. Can you talk about who this treatment option might be appropriate for? 

Dr. Nadeem:

So, yeah, just to kind of give folks background, CAR T-cell therapy is a form of immunotherapy, where we take out an individual’s T-cells and then re-program them, essentially, to recognize myeloma cells. Right now there’s two approved CAR-T products for multiple myeloma, both in the relapse refractory setting. It’s really for patients that have had four or more lines of therapy.  

So, that’s a lot of different combinations that we currently have available. Those therapies stop working before patients are actually eligible for CAR-T cells at the moment. Both of these CAR T-cell products have been gamechangers in terms of improving prognosis for patients.  

The good thing about CAR-T cells is that it is a one-and-done treatment. So, patients, when they go through that initial phase of therapy, they are then off therapy, although we are now starting to study certain therapies that we may administer after CAR-T cells to get them to last even longer than they currently do, but that’s still in, for example, that’s one of the clinical trials or many of the clinical trials that are currently ongoing now, to try to answer that question.   

So, a lot of patients can be eligible for CAR-T cells. They have to have the prerequisite amount of therapies. Again, there are some sort of baseline fitness characteristics that we look at for patient’s ability to tolerate it. But as a whole, I consider CAR T-cell therapy more broadly applicable to myeloma patients than compared to, let’s say, a stem cell transplant.   

Katherine:

How has this therapy revolutionized myeloma care? 

Dr. Nadeem:

Yeah, before the first approval, now a few years ago, in this space we didn’t really have anything like this to offer patients. So, many of the combinations and other compounds that were in clinical trials would have a response rate somewhere around, let’s say, 30 percent. So, 30 percent of patients may respond to that therapy in that space, and that may only last a few months, and that was considered successful not that long ago. Now, with CAR T-cell therapy and bispecific antibodies, these therapies are highly efficacious.  

You see response rates of 70 to 100 percent in some of these immunotherapies, and what that’s translating into is patient’s disease staying away for a year or two years, even three years in some of these clinical trials. And again, this is completely unprecedented compared to what we had before.   

Katherine:

I understand that there are a number of clinical trials for different types of CAR T, or even using it earlier in the disease. Can you share updates in CAR T-cell therapy research? 

Dr. Nadeem:

Yeah, so, exactly as you pointed out, there have been trials already, actually, that have been completed, Phase III studies looking at CAR T-cell therapies in earlier relapses.  So, patients that have had either one of two lines of therapy. 

Both our CAR-T therapies have been compared to standard of care in that space and have shown superiority, and this is something that we all have been kind of waiting for to see if you deploy it earlier, perhaps you’re going to see even greater benefit, and that seems to be the case in some of these trials, and now we’re awaiting, hopefully, approval of some of these CAR T-cell therapies to be administered earlier because in fifth line, it’s very different than treating patients in second or third line, which I think will really vastly improve our ability to deliver this therapy to many patients, as it can be quite challenging for patients that are in fifth line, to allow them to go through the process of CAR-T cells and then having them be administered.  

I was looking at it head-to-head with stem cell transplant, as I mentioned before, and this is in the context of quadruplet and induction therapy followed by either CAR-T cells or stem cell transplant, and then followed by maintenance therapy. So, really trying to see if I can overcome what we typically have achieved with stem cell transplantation. 

We also are doing some studies even before that. So, patients, again, in high-risk smoldering myeloma, which we know have an increased risk of developing newly diagnosed disease in the next few years, perhaps that could be the time where we can give some of these immunotherapies, and that’s some work that we have going on at our center. 

Katherine:

Well, another therapy that has emerged in myeloma is bispecific antibodies. What patient type is this therapy right for? 

Dr. Nadeem:

So, bispecific antibodies are great because they’re off the shelf. What that means is that CAR-T cells, we first have to collect the T cells and we then have to send them off to be manufactured, and that manufacturing process can take up to a month, sometimes even longer, for some of the current available CAR-T products. And then, after the cells are returned to the facility, we then give usually three days of chemotherapy to try to suppress some of the immune systems of the patients. So, that way, when the cells are administered, they can expand robustly and do essentially what they need to do. 

So, that whole logistical process can take a couple of months by the time you identify somebody for CAR-T cells and then, from that moment until they can actually be treated. With bispecific antibodies, if we think somebody’s ready to go, you can basically get it as soon as we can have somebody ready to go either in our clinic or on the in-patient facility. So, they’re much easier. They also utilize T cells to attack myeloma cells. We now have three approved bispecific antibodies. Two of them are targeting BCMA, the same exact target that we have in CAR-T cells, and one of them is now targeting a new target called GPRC5D, which is also highly expressed on myeloma cells.  

So, having all these bispecific antibodies available is excellent because patients can have access to them a lot faster and now we’re trying to answer the question of sequencing. Can you give bispecific antibodies after CAR-T cells for example? Can you give one bispecific antibody after another, especially if there’s a different target that we now have available? 

As a whole, though, bispecific antibodies tend to have lower response rates than CAR-T cells, particularly Cilta-cel (Carvykti), which is cilta-cel that has a very high response rate of close to 100 percent.  

Most bispecific antibodies have response rates somewhere around 70 or so percent, so about two-thirds of patients respond to these therapies, again, in that fifth line or four or more lines of therapy. So, in that space, that’s the response rate. And across the board, generally speaking, patients benefit from these bispecific antibodies approximately a year on average. Some of the studies have shown longer benefit, and it also depends somewhat on response to therapy.  

Patients that have a really deep response can go even way longer than that. So, it is quite mixed in terms of how somebody may do on these bispecific antibodies, but those are the numbers.  

Katherine:

Well, it sounds like bispecific antibodies have really transformed myeloma treatment options.  

Dr. Nadeem:

Absolutely, and what goes hand in hand in this.  

I mentioned the logistics of CAR T, but then there’s also the supply and availability of CAR-T cells. Since the approval, the demand for CAR-T cells has been very high because of all these excellent results, but the supply really hasn’t been there. So, even at a center as busy as ours, we can only treat a handful of patients with CAR T-cell therapies compared to bispecific antibodies, where that is essentially an injection similar to many other approved myeloma agents that you can just readily treat patients with. So, CAR-T cells, while I think, again, have higher efficacy, with that comes slightly higher toxicity as well. It’s a very different kind of treatment program.  

And then, patients get a treatment-free interval, which you don’t see yet with bispecific antibodies. On the other hand, bispecific antibodies are readily available, slightly lower response rates, slightly lower toxicity when it comes to at least the traditional T-cell directing toxicities. And then you have, again, the readily available nature of it, which I think is hugely beneficial for patients.  

Katherine:

You talked about some specifics regarding bispecific antibodies, but are there updates in bispecific antibody research that you’d like to share? 

Dr. Nadeem:

Yeah, so, again, kind of following the theme of what we just said about CAR-T cells, can you bring these antibody therapies earlier? And there’s ongoing trials now looking at it in newly diagnosed multiple myeloma and early relapses, and then we presented our data at ASH this previous year looking at it in high-risk smoldering myeloma. We treated patients with teclistimab (Tecvayli), which is a BCMA bispecific antibody that is approved for relapse refractory patients. And what we demonstrated in that study is that people that got Teclistimab had a 100 percent response rate with an MRD-negative rate. So, kind of as deep of a response as we can measure, also at 100 percent.  

So, this is something that we had not seen before. When their immune systems are a lot healthier, they may benefit more. So, hopefully we’ll see confirmation of these results in other trials.  

Particularly in the newly diagnosed space because we do think that these antibody therapies have such huge potential to treat patients, and then hopefully we’ll have durable responses. So, I do think that some of this paradigm may shift over the next few years, and then there’s also combinations that are currently being studied: combinations with traditional myeloma therapies, such as monoclonal antibodies, other immunomodulatory agents, or proteasome inhibitors. All these combination trials are now ongoing to see can you improve upon some of those numbers that I highlighted before with single-agent bispecific antibody therapy. 

Katherine:

Oh, I was just going to ask you the next question, which is are there other emerging myeloma therapies that are showing promise? 

Dr. Nadeem:

Yes. So, I think over the last few years, most of the buzz has been with these immunotherapies. And, again, more work to be done there to see whether combinations, different schedules, different targets, different types, will show more and more benefit in each of these myeloma disease settings.  

But we also have simultaneous development of other agents that are not in this sort of immunotherapy T-cell redirecting therapy realm. We have newer versions of our classic immunomodulatory drugs, such as lenalidomide (Revlimid) or pomalidomide (Pomalyst).  

We now have their next generation agents, called CELMoD drugs and there’s two of them in development. One of them is called iberdomide; one is called mezigdomide.  

These are, again, kind of building up on the success of some of these previous therapies that are kind of cornerstone therapies for myeloma patients and because these are essentially better agents, they’re more targeted, and they also have greater response rates as single agents and as combinations.  

We’re hoping that these would be approved in the not-so-distant future and then perhaps will replace some of these immunomodulatory drugs that we have currently utilized in newly diagnosed and relapsed myeloma. Essentially what this means is things are just getting better and better and better as we get newer versions of some of these therapies. So, those are, I would say, kind of next in line in terms of hopeful approvals.  

And then we’ll add to some of the options that we have for myeloma patients.  

Katherine:

How can patients and care partners stay informed about the latest myeloma research? 

Dr. Nadeem:

Yeah, it’s a lot of moving parts all the time. From one six-month interval to the next, you tend to have nowadays perhaps some drug approvals, which is amazing, but if not updates of all these sort of combination trials, etcetera, of where these things are going. I think kind of talking to your physician, obviously, about some of these updates is really critical. As I mentioned before, having a roadmap in your mind about what the myeloma therapy for you might look like going forward, wherever you are in your disease state, is always important because it gives you time to sort of think about it, learn about it, prepare for it.  

Some of these therapies really require an effort from the patient and their caregivers because, for example, for CAR-T cells. If you’re not near a center, you may have to relocate for a month.  

And it’s very difficult, and we fully understand that and try to help as much as we can, but that’s the kind of commitment that it takes. So, talking to your physician, obviously content like this, reviewing this as much as you can. Online patient support groups are great because you learn from the other patients’ experiences. So, the good news now is we have so many channels of communication, but you have to in a way, in the end, discuss with your physician and verify things you may find on your own.   

Katherine:

Exactly, yeah. You want to make sure you’re getting facts rather than fiction.  

Dr. Nadeem:

Yeah. That’s right.  

Katherine:

Well, Dr. Nadeem, we’ve been hearing the term personalized medicine more frequently in recent years. How would you define personalized medicine for myeloma, and how can patients access this type of care? 

Dr. Nadeem:

Yeah, personalized medicine or precision medicine is a term that we’ve really sort of used for many oncologic conditions over the last decade or so. I would say, for multiple myeloma, in terms of identifying a target within the myeloma cell that’s unique to the patient.  

And then deploying a certain therapy to that patient because of that target is still lacking. We do have one example where patients have, for example, an 11;14 translocation, which we see in about 15 percent of myeloma patients.  

There’s an agent called venetoclax (Venclexta) that is very active against that particular cohort of patients, although that is still not approved to be used, but that’s one example where that agent specifically benefits that type of myeloma. Other than that, most of the therapies that we have benefit essentially everybody with myeloma, which is great, but it’s not so personalized.  

Where I would say there’s the most personalization happening now, at least in my practice, is looking at which types of therapies an individual patient may receive. What I mean by that is if somebody’s in an excellent response, with quadruplet-based induction therapy, I have a very real discussion with them about the pros and cons of stem cell transplant. We make those decisions in real time depending on how the patient doing, depending on how their response is.  

And then kind of deciding a whole kind of what are the kind of risks and benefits and what makes sense for that individual patient. Similarly, when you go on to maintenance therapy, maintenance therapy means that after you’ve gone through the initial phase of your myeloma therapy and the disease is under control, what type of therapy can we keep you on to keep it under control for as long as possible? Historically, that has been lenalidomide or Revlimid. Now we’re adding drugs such as daratumamab and other agents to Revlimid to see if that can further prolong the response to that initial therapy.  

So, all those decisions are so individualized that you have to discuss with your provider what makes sense for you and what are the pros and cons of doing one approach versus the other.  

Katherine:

Well, if we’re talking about in-depth testing, how do the results of that testing affect treatment options? 

Dr. Nadeem:

So, right now we use conventional blood tests to get a sense of response in the vast majority of patients. That includes the serum protein electrophoresis and the serum free light chain assay.  

Most patients have detectable levels of these proteins, abnormal proteins in the blood at diagnosis and then you can follow them using a blood test. There’s a subset of patients that have disease only that shows up on scans. So, we then kind of incorporate some of those scans and then, also, utilize the bone marrow results both in the beginning and in subsequent analyses to kind of give a big-picture composite response assessment for that particular patient. Nowadays, there are also other tools that we’re using, such as MRD, or minimal residual disease.  

That is a test that is done on a bone marrow biopsy to determine, if you don’t have detectable protein in the blood, do you have myeloma cells present at the deepest level possible? And if you do versus if you don’t, trials have shown that there is a difference in terms of prognosis. Now, while that hasn’t fully been utilized yet to make treatment decisions in patients that are not on clinical trials, we do get prognostic information out of it, and nowadays, more and more of those trials are using these MRD tests to determine what to do with treatment.   

And I think that’s how it’s going to be in the future. So, having those extra tests available but, again, important to discuss with your provider what is the utility of this test. How are we going to use this information for your individual case to make some decisions? 

Katherine:

What questions should patients be asking their provider about a proposed treatment plan?  

Dr. Nadeem:

Yeah. I think because myeloma therapy’s so nuanced and much of this is still in clinical trials or under investigation about what to do with some of these results, I would say, as a whole, it’s important to know which tests the physician looks at to determine how you’re doing, and kind of what their assessment of that result is. So, for example, if somebody’s had a 50 percent reduction in the amount of abnormal protein in the blood, is that sufficient, or should we be aiming for a number that’s much higher than that? 

Some of that depends on kind of where they are in their treatment course, but that’s a very sort of reasonable question to ask your physician is that where do you see my response now, let’s say six months into therapy, and is this adequate, and what is now, after we have all this information, what is my roadmap going forward to try to keep this disease in check? 

Katherine:

Yeah. Well, that’s great advice, Dr. Nadeem. Thank you. PEN has also created a downloadable office visit planner to help you organize your thoughts and communicate effectively with your healthcare team. You can find these at Powerfulpatients.org/myeloma.  

I’d like to turn to self-advocacy, Dr. Nadeem. Why is it so important that patients engage in their care treatment decisions? 

Dr. Nadeem:

Yeah. As I mentioned, myeloma therapy is so individualized now and we can sit here, look at the trial data, get very into the weeds and technical about this therapy with this approach as X or Y higher response rate.   

Or MRD-negative rate, but in reality, we’re dealing with people and we’re dealing with people that have lives. They have all their priorities, and until you share that with us, it’s very difficult for us to know exactly what’s important to you. So, what I may consider to be kind of the “best therapy” for you may not make sense for you because of all the priorities that you may have, and I think it’s so important to advocate for yourself and not be afraid to bring that up to your physician because I think many patients kind of hold that stuff in for a long time because they don’t want it to impact their care. But I would argue the other way around.  

Tell us. Tell us exactly what you prioritize. Tell us if you can’t be out of commission for work for X amount of time because of a stem cell transplant. We now have options. We now have options for patients because of all these amazing new therapies for myeloma and we can come up with a very individualized treatment plan for you based on your priorities.  

Katherine:

If a patient is feeling like they’re not getting the best care or they’re uncomfortable with the care they’re receiving, what steps should they take to change that?  

Dr. Nadeem:

Yeah, I think that’s very difficult because this is a complex system. Medical systems are getting even more and more complex. They’re busy. Everybody’s busy: busy offices, labs, radiology. We’re all feeling that. It doesn’t matter where you are. So, I think it’s important to raise those concerns, number one, to your practice that you’re being seen at because they would like to see that feedback, right? So, kind of see what is something that they can perhaps improve upon. I think it’s always important, like we just said, to advocate for yourself and raise some of these issues and not be afraid of that.  

We’re all in this together, right, so I think ultimately, we’re all trying to take the best care of you and we would need to know which part of that may or may not be working so well.  

Katherine:

Let’s get to a few audience questions that we received prior to the program. This one is from Rita. “Is there an age limit on CAR T-cell therapy?” 

Dr. Nadeem:

So, no, there isn’t. A lot of age-related cutoffs that we’ve historically used for transplants or even the CAR T originally don’t really apply because we all know there’s patients that are in their late 70s that may be more fit and robust than somebody in their 50s. We see this all the time. So, frailty is something that we assess quite a bit in patients in determining whether they can handle some of the toxicities that may come from these therapies. So, there’s no age cutoff.  

Again, we look at certain other medical problems you may have, how fit you are, your organ function and things like that, but ultimately the goal is can you tolerate the chemotherapy you get before CAR-T cells and then can you tolerate some of the acute toxicities of CAR-T cells, such as the cytokine release syndrome, some risk of neurological toxicity, things like that. All of those are usually short-term, and if you feel confident that we can get you through that, then you’re eligible.  

Katherine:

Yeah. Laura sent in this question: “I’m considering bispecific antibody therapy. I know some of the side effects are similar to CAR T-cell therapy. Can you share the pros and cons of bispecifics and how it compares to CAR T?” 

Dr. Nadeem:

Yeah. I think we mentioned earlier that as a whole, they’re very similar. They’re both T-cell re-directing therapies, in many circumstances, with the same exact target of the myeloma cell, but because this isn’t a cell infusion – this is a cell injection – that you receive that redirects your T cells to the myeloma cells, you tend to see a little bit of a lower toxicity signal when it comes to the cytokine release syndrome incidents and severity. You see lower neurological toxicity, usually, than you do with CAR  T-cell products as a whole.  

With that comes slightly lower efficacy than you see with at least some of our CAR-T products, but if you respond to therapy, then the durability of response can be as good as you can achieve with CAR-T cells. One thing to note about the bispecifics, though, is that it is continuous therapy, so you are getting it on some regular schedule. Right now the approval is for it to be given weekly and then go to every two weeks after six months of therapy if you’re basically in a good response.  

A lot of that is to try to mitigate the risk of infection. So, that is one of the biggest things that we have seen with bispecifics more so than CAR-T cells. Because it is continuous administration of these therapies, that really suppresses your immune system significantly, and infection rates are quite high. So, we typically give other ways to try to mitigate that using immunoglobulin infusions to try to boost up your immune system. Typically, we do that once a month for patients, making sure you’re on the right prophylactic medications and then really adjusting the therapy and the schedule to you depending on your tolerability.  

So, as we said before, it’s an excellent option. I think bispecific antibodies are going to be the mainstay of myeloma therapy going forward because CAR-T cells, again, we can’t really treat everybody with CAR-T cells just simply because of the dynamics of how the process is. So, having the bispecific antibodies available for patients is excellent.  

Katherine:

Thank you for this information, Dr. Nadeem. And please continue to send in your questions to questions@powerfulpatients.org and we’ll work to get them answered on future programs.  

We’ve definitely learned today that the field of myeloma care is advancing quickly. As we close out the program, what would you like to leave the audience with? Why are you hopeful? 

Dr. Nadeem:

Yeah. I think you all can see the tremendous progress that’s been made and, again, I still think it’s sort of the tip of the iceberg. These immunotherapies that are really showing this kind of activity, we’re just learning about them, and we’re going to improve them, not just the way we administer them. We’re going to make them even better and better and better and our hope is that a cure is not so far in the future. And perhaps even now we can cure a subset of patients if we deploy some of these therapies in the right person at the right time. So, I think that is really what I am hopeful for, that we have all these options available.  

Now it’s up to us to figure out which one fits in where and then, as we do that, hopefully we’ll see even better and better outcomes. And my hope is, over time, that this is a disease that we can cure at least in a subset of patients, which means that they get fixed duration therapy with whatever that we have.  

And then they’re done, and then hopefully never have to have therapy for this disease because it’ll be gone, and then, in patients that develop a disease relapse, we then treat them with some of these other agents. So, this is starting to hopefully mirror what we see in other blood cancers, such as lymphoma, for example, where you give the initial therapy and cure a subset of patients. Hopefully we can get there with myeloma in the not-so-distant future.  

Katherine:

It’s a very promising outlook to leave our audience with. Dr. Nadeem, thank you so much for joining us today. 

Dr. Nadeem:

Thank you so much for having me.   

Katherine:

And thank you to all of our collaborators. 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 today.  

PODCAST: Thrive | Considering CAR T-Cell Therapy for Myeloma? What You Should Know

 

Dr. Beth Faiman, a myeloma expert and researcher, discusses factors that should be considered when deciding to undergo CAR T-cell therapy, advice for preparing for and after the process, and why a good support team is essential. Dr. Faiman also shares research updates in CAR T-cell therapy, and alternatives options to this myeloma treatment.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

See More From Thrive CAR T-Cell Therapy

Download Resource Guide

Transcript:

Katherine Banwell:

Welcome. I’m your host, Katherine Banwell. As patients navigate their myeloma care, it’s essential for them to feel formed when engaging with their care team. That’s why the Patient Empowerment Network developed the Thrive series, to share support and educational resources so that patients can feel confident at every stage of their care. In today’s program, we’re going to hear from a renowned myeloma expert as we discuss CAR-T therapy. Before we meet today’s guest, 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, joining us today is Dr. Beth Faiman. Dr. Faiman, welcome. Would you please introduce yourself?  

Dr. Beth Faiman:

Thank you so much, Katherine, and it’s such an honor and a pleasure to be here today. My name is Beth Faiman. I am a nurse practitioner and a PhD researcher at the Cleveland Clinic in Cleveland, Ohio, where I have worked since 1994, in the field of myeloma mostly. Thank you.  

Katherine Banwell:

Excellent. Thank you so much for joining us today. As I mentioned, today’s program is part of our Thrive series. So, from your perspective, what does it mean to thrive with myeloma?  

Dr. Beth Faiman:

So, to thrive with myeloma is something that when I started managing patients in the 1990s individuals didn’t live very long, maybe two to three years, because we did not have good therapies. Now, we talk about living well with myeloma, thriving with myeloma. It just makes me so happy. I think for plants. I think of flowers that can grow in the right environment. I had a plant in my office recently that somebody had gifted me, and it sat there and tried to soak up the little bit of sunlight that it could muster and just wasn’t doing well.  

So, I brought it home and I put it in a big window. That plant is beautiful now and I just love looking at it and thinking about it. And it reminds me of how if you’re in your right environment with multiple myeloma you surround yourself with friends, families, coworkers, church friends, or places of worship, then you can really thrive in that environment or you can grow. And even though you have a cancer diagnosis, that is not – and I hate to use the D-word – a death sentence anymore. You can live many years and live well with myeloma in the right environment like my little plant.  

Katherine Banwell:

That’s a great idea to think about. Thank you. Well, we’ve covered this in recent webinars but it’s worth sharing again. Can you give us an overview of the process and timeline for someone choosing CAR T-cell therapy for myeloma treatment?  

Dr. Beth Faiman:

Yes. So, CAR T-cell therapy, when we first started discussing this in the mid-2000s, I thought this was science fiction.  

Taking somebody’s own cells, engineering them to be fighters against the cancer cells. I thought it was science fiction. But now, we have two FDA approved therapies for multiple myeloma. It’s Ide-cel, which was approved in 2021 and Cilta-cel, approved in 2022.  

Now, the process is lengthy and I know you’ve covered this before but from my perspective, I think if you want to take something home form this webinar, plan early. So, you need to have three prior lines of therapy as a myeloma patient to qualify for this treatment. But you can start planning for it ahead of time.  

So, it’s not available in every center. So, you want to start researching what the closest center would be for you to have this therapy. Many different patient support networks will have these centers on their websites. So anyhow, you find out.  

“Okay. I want to learn more about a CAR T-cell therapy.” Then you have to meet with a specialist. So, you get that education, have that referral, and meet with a specialist at a center that does CAR T-cell therapy. And that might be where you got your initial transplant if you’ve then returned to the community. After that, then we find a slot for you when it’s ready. So, there is that process of financial, physical, social things that are checked in the background. You meet with a social worker, nurses, etc.  

Once you’ve confirmed that you’re going to go through this process – now, it might be three, six, nine months in the future, if you’re a planner – but if you want to just gain information, it’s that harvesting and storing of the cells. That’s where I try to tell people age is not a number. You can be at any age and you qualify for this therapy. We’ve had people well into their late 70s to early 80s who have gotten these therapies.   

Long story short, it’s a process.  

You get your cells harvested and then while they’re being manufactured into fighters, they take the T cells from your blood through an apheresis machine and freeze them, send them off, make them into fighters, and then reinfuse them in your bloodstream. It’s a long process. It can take anywhere from two to three months from when you decide it’s right for you.  

Katherine Banwell:

Well, thank you for explaining that. That’s really important. It puts into perspective. It’s a big undertaking. But also, quite manageable, I think, right, with the right team and support. Who are the members?   

Dr. Beth Faiman:

Absolutely. The family members, friends, and, of course – I like to use the words the multidisciplinary team. That’s your physicians, your social workers, nurses, nurse practitioners like me, pharmacists, and then all your other specialists.  

So really, mounting that team from diagnosis and throughout your whole journey as a myeloma patient can really enrichen your life and help you thrive in that environment.  

Katherine Banwell:

Yeah. It sounds like there’s a lot of support for someone going through this process and that the care partner also plays a critical role on the care team, right?  

Dr. Beth Faiman:

Oh, absolutely. So, I am a big advocate for care partner though not everybody has a caregiver. So, it can be a formal caregiver, somebody’s spouse, daughter, son, significant other. Or it can be an informal caregiver. So, I’ve had patients that – because you need to have a care partner to qualify for CAR T-cell therapy, because patients need to be monitored for about 30 days afterwards. So, that might be pulling in friends from your place of worship, people from the community, and then also people from the cancer center.  

Some of the larger centers that do the CART-cell therapy have a network setup where you get this list of people that have volunteered to drive you to appointments or maybe arrange for Uber help to drive you back and forth. I am not plugging Uber or Lyft, but a rideshare company. And so, finding out those resources can help anyone – just about anyone – access these CAR  T-cell therapies, because you can have a long-term remission. Think about somebody who’s been through treatment A, B, C, or D and then now, “Gosh, maybe my life is going to be shortened.”  

Not necessarily. If this is the right recipe to control their myeloma then they can get 11, 24 months off of everything – just antibiotics – and be monitored. And so, it puts them at a position where if you can get the care partner, get a care team, to support you then you can have access to a potentially life extending with good quality of life therapy.   

Katherine Banwell:

Yeah. I’m sure many of our viewers today are wondering who the therapy is right for and when is it most appropriate in the course of myeloma? Could you address that?  

Dr. Beth Faiman:

Yeah, absolutely. So, currently, you have to have had three prior lines of therapy with drugs such as a CD38, which is – daratumumab (Darzalex) is a name of a medication.  

You have to have a drug such as lenalidomide (Revlimid) as well as a drug like bortezomib (Velcade). And you have to have had three lines of therapy. So, that’s how you can access the therapy. But if you’re willing to participate in a well-designed clinical trial there are studies with CAR T-cell therapy earlier on.  

So, one of the things that we’re advocating in the myeloma world is clinical trials. We haven’t gotten to where we are in 2024 with the advances in sciences, the advances in living longer and living well with myeloma, without the brave people before us that have participated in clinical trials. 

So, people who it’s right for would be if they qualify for a clinical trial before their third or fourth line of therapy or if they’ve had three or four prior lines of therapy. And there are other points to that which I’m sure we’ll talk about later on.  

Katherine Banwell:

In your opinion, what are three key considerations that myeloma patients and care partners should think about related to the CAR T-cell therapy approach?   

Dr. Beth Faiman:

Oh, gosh. Well, I would like to say that always when you’re selecting a therapy, think of the physical, the financial, and the social implications of that therapy. So, physically is the medication too strong for you? Are you too weak to take it? Or is it just right for you? So, finding the right medication for the right patient at the right dose at the right time. So, the physical component. The financial component is also very important. So, maybe your insurance now won’t cover it but then there’s open enrollment in Medicare towards the end of the year or you can find financial support reimbursement through many of our generous organizations that will provide grants for certain medications.  

And then, the social. Do you have a care partner, as we discussed? The importance of being monitored for 30 days. If you don’t have a formal care partner, is there some system that we can help support you through so that you can have the different supports throughout. It’s not only that beginning part where you’re gaining the information – and I think of it like a timeline. The beginning part, you’re thinking about gathering information to the – in that process of getting yourselves back because of the side effects, which I think have been talked about in a prior webinar.  

And then, the post-monitoring where you go back to your community, taking antibiotics, antiviral medications, etc., to keep you living well longer. So, it’s a process.  

Katherine Banwell:

Well, it’s great advice, Dr. Faiman, thank you. I’d also like to add that if you’re considering CAR T-cell therapy, the Patient Empowerment Network has a wealth of information on this topic, including resource guides and interviews with experts like Dr. Faiman. 

And you can find those at powerfulpatients.org/myeloma. So, Dr. Faiman, when a patient is talking with their care team about CAR T-cell therapy, what questions should they be asking to help determine if CAR-T is even right for them?  

Dr. Beth Faiman:

Katherine, that’s an excellent question. So, let’s just say that somebody from Patient Empowerment Network heard about CAR T-cell therapy for myeloma and then sought out a local institution that might be conducting that procedure. So then, they come for that visit and what you mentioned was just spot on, getting a list of questions together. What we do at my institution, as well as many throughout the country, is a process called shared decision-making.  

You might’ve talked about this on prior webinars, but shared decision-making occurs when that healthcare team, such as the physician, nurse practitioner, pharmacist, whoever, shares information with the patient and their care partner.  

You mutually share information to arrive at a decision. So, many studies have been done on shared decision-making. It’s done in many different areas. And so, through that sharing of information, you might think of different questions.  

Some of the things that I try to proactively offer – we all have our list of things that we educate our patients on, but some of the things I proactively will recommend to patients and their care partners when you’re seeking an opinion at these centers is, “How long will I be sick? What are the biggest side effects of the medication I have to worry about?” Asking your care team – I know it sounds silly, but are they aware of all your prior health concerns, especially if you’re coming for an evaluation.  

Maybe you have peripheral neuropathy where you have numbness and tingling in your fingers or toes or a history of kidney disease. Your kidneys look fine now but maybe a few years ago at the myeloma diagnosis the kidneys had a temporary failing and now they’re better so they’d want to protect you with future medications. How long will you have to take medications after the CAR-T procedure? There’s antiviral medicines, antibacterial medications, and medications called IVIG, which strengthens your immune system.  

And then, finally, asking about the infection protection afterwards. Do you have to get vaccinated again against pneumococcal, shingles, and all of those other things that we do. The cellular therapy guidelines suggest timepoint for one, three, five, etc., months after CAR T-cell procedure to get revaccinated. So, who’s going to do that for you?  

How are you going to know what to get? So, make sure that they give you a timeline, calendars, and set expectations for what you need to do as a patient and then you’ll help them set expectations for what they need to do to provide you the accurate education.  

Katherine Banwell:

Well, talking about what to expect after CAR T-cell therapy, would you tell us what some of the potential side effects are?  

Dr. Beth Faiman:

Oh, absolutely. So, CAR T-cell therapy – again, it harnesses your immune system using your T cells. Your T cells are so important in your immune system to be programmed as fighters. And as people age, or as long as – after they’ve had myeloma or other kinds of cancers, those T cells just don’t work as well. So, what we want to do is engineer them and program them with what we call a viral vector to be fighters. So, those T cells, as I mentioned, are harvested, stored, and then manufactured to go. 

And I tell people it’s like that Pac-Man video game. It goes around in your bloodstream just kind of eating away at the myeloma cells. So, you don’t take any medications. You don’t go in for IVs every week or twice weekly, or taking pills at home to treat the myeloma. It’s what we consider a one-and-done thing. So, if it works for you, it can keep you in remission for quite some time. But if it doesn’t work then there still are other therapies down the road.  

So, the CAR T-cell therapy is something that is an option but there are other therapies out there in many cases. There’s something called a bispecific antibody. There are three currently approved for multiple myeloma now. So, maybe a CAR T-cell therapy doesn’t seem right for you because you’re not in a good remission or the cancer’s too active right now so you don’t have the time to wait for manufacturing of the cells and putting them back in your bloodstream.  

Those bispecifics will fill that gap. So, when you’re discussing the options, aside from clinical trials and other drugs, the bispecific antibody is very similar. One of the things that I wanted to highlight is that nowadays we’re into these things called sequencing. So, we’re trying to figure out what order to give these super effective drugs. Should we give the bispecific antibodies first or should we give the CAR T-cell therapy first? And in most centers, if you have time to wait and you’re planning, the CAR T-cell therapy is right for most people and then the bispecifics would come later.  

Katherine Banwell:

All right. So, after CAR T-cell therapy is completed, what potential side effects might people experience, and what should they look for?  

Dr. Beth Faiman:

Absolutely. I think of things in short-term and long-term side effects. So, the short term, you’re going to be admitted to the hospital and you have a risk for – when we get those T cells back – that cytokine release syndrome, or it’s abbreviated CRS – where you’re body’s immune system’s fighting.  

I tell folks it’s kind of like if you got a vaccine for a flu vaccine or pneumonia and you had a reaction it’s just way worse. So, you can get a high fever – the big first sign of this CRS. Usually, the providers will jump in with giving you a medication called tocilizumab (Actemra) or a similar drug that blocks IL-6, which is a chemical that is triggered when we get the CRS. And then, it stops those symptoms. And so, most of us know how to do that and will approve your insurance to get access to that tocilizumab or similar drug when we approve your CAR T-cell therapy.  

So, that CRS can get you really, really sick. You can get low oxygen levels in your blood. You can get a high fever and you can drop your blood pressure. But most CAR T-cells centers, the nurses and the staff are very well-trained to monitor this every eight hours, in most cases.  

Another rare side effect we worry about is ICANS and it’s a neurotoxicity kind of thing.  

It can be with CRS or without CRS. But they’ll ask you to do things like write your name on a piece of paper every eight hours or tell me – draw a clock or count backwards from 100. And so, if you have any deviation, even minor, from what you reported back beforehand then we worry about neurotoxicity. Now, that’s short term but that’s the reason why you can’t drive a car for 30 days is because it could be delayed. 

The CRS can start with the one thing, the ide-cel usually occurs within one day so most people are admitted to the hospital for that CAR T-cell therapy. The Cilta-cel, it onsets to about seven days. So, some people get the cilta-cel outpatient and then are monitored daily, whether in person or through virtual telehealth monitoring.  

But at any rate, those are the short-term. Long-term, we worry about low blood counts maybe for the first month afterwards. And then, those will come back to normal. And then, we worry about infection. So, I mentioned the antibacterial, antiviral, which is usually a medicine called acyclovir (Zovirax), which most myeloma patients will have been on anyhow. And then, that IVIG to protect against viruses and bacteria when your immune system is so low. 

But fortunately, if we control the CRS, it usually comes with the CRS, although it can be independent. We try not to give steroids, because we don’t want it to interrupt the CAR T-cell process. But many institutions will give that tocilizumab for ICANS. And if that doesn’t get better then they’ll give you a steroid, such as dexamethasone (Decadron). 

And so, that will usually reverse itself pretty quickly. Longer term, after 30 days, you can get with the Carvykti, particularly something called Parkinsonian things where you can get a little bit shaky or something like that. Again, it’s very rare and I have had hundreds of people who have undergone the CAR T-cell procedure at my institution. And knock on wood, fortunately, I’ve not seen first-hand that side effect. And I think it’s because we’re so good now at treating the – preventing the ICANS and CRS as best as we can while they’re inpatient and doing real close following.  

One other thing I want to note is if somebody who’s watching this does go in the hospital for any reason, get up and walk around and stay strong, as well as you can, during the procedure. You might be bored if you’re in the hospital anyhow, but try to stay as strong as you can in the hospital. It’ll help your post recovery for sure.  

Katherine Banwell:

Well, what about more mild side effects like fatigue and changes in appetite?   

Dr. Beth Faiman:

Absolutely. So, the fatigue and the changes in appetite are generally mild for most but I see it, in my experience, if your myeloma’s acting up really quickly, if you’re having a rapid disease progression, the medications that we give you to control the myeloma during this bridging therapy phase might cause some of that as well, not necessarily the CAR T-cell process. But think about it. We’re using your own cells engineered to be fighters.  

And so, that first month or two is probably when you’re going to be the most tired as your body is being programmed to fight against the myeloma cells. That fatigue tends to get better. And as I mentioned just a moment earlier, the importance of just walking around in the halls, getting out of bed when you’re in the hospital, that can really help your post recovery. It doesn’t seem like much, but there have been many studies about how muscle mass declines, energy declines when you’re hospitalized.  

And we want you to be as strong as you can and thrive as much as you can for when you’re out you can then do the things you want to do at a quicker pace.   

Katherine Banwell:

Right. That’s great advice. Beyond monitoring of any issues, what can someone expect related to returning to life as they knew it before the diagnosis? Is there a timeline for resuming lifestyle and activity?  

Dr. Beth Faiman:

Yeah. So, I should say I because it’s from my perspective. I am a real strong advocate. I tell people to do what you feel like you can physically do. We know that myeloma can affect the bones and put your bones at risk for breaking and so we give you medicines to protect it. So, I do put some restrictions however on physical activity in terms of, “I don’t want you to bench press 40 pounds or 20 pounds,” in most cases. And depending on what the bones look like on x-ray, I’ll even restrict it to about five to 10 pounds.  

If you think about it, that’s a bag of potatoes. So, you don’t want to put too many restrictions on for everybody. But talk to your healthcare provider about what your specific restrictions are with physical activity. Because I don’t really put any restrictions on but I encourage things like riding a bike, especially a stationary bike in your own home, so that if you fall off – hopefully, you won’t fall off a stationary bike. But if you injure yourself, then you’re able to be in a place that somebody can help you.  

But riding a bike. Also, exercising in water. Water therapy is a great weight bearing exercise and there are times of day where you can go when the YMCAs or YWCAs aren’t as busy – or community centers. So, you’re less at risk for bacterial or other illnesses. But during that first month, I try to limit their exposure to people because you’re at risk for the different viruses that are all over the place, the bacterial infections. 

So, that first month is the critical period where I try to say, “Okay, try to lay low. Let’s get you through this period. Your immune system will start getting stronger on its own after this period.” And then, that month two you start feeling like doing more. You go to the grocery store. You maybe go to eat out at a restaurant but pick a time of day that’s less busy. So, go for an early dinner. There’s no shame in eating at 5:00 p.m. if you want to go out. And then, get a table in the corner with your own wipes. And so, that’s where your immune system is getting stronger. 

And then, by month three, I think most people will feel much, much better and much, much stronger. And if you can keep moving throughout this whole time, then you’ll be stronger on the way out.  

Katherine Banwell:

Dr. Faiman, from what you’ve described, undergoing CAR T-cell therapy can be a very intense process. Why would someone consider this option over another myeloma treatment option?  

Dr. Beth Faiman:

Yeah. So, the CAR T-cell therapies have really transformed myeloma, in my opinion.  

When we first started using CAR T-cell therapies, there was a long wait list because people who had had three, five, seven, 10, 12 prior therapies, they had very few other options. So, we had ethically assigned scores to people as to who – we’d get one or two slots a month and then we’d have 80-some people on this list. And we’re thinking, “How do we allocate who’s going to get this therapy?” And it’s because you can have a nice, long remission off of all therapy.  

It’s a great, great option for most people. Again, I would hope that we can get this moved further into the disease trajectory. There are actually two studies. One was a KarMMa study. It was published in the New England Journal of Medicine in 2023, early part of 2023.  

And it showed that when people get this therapy earlier, the Ide-cel first, you can have a longer remission. So, we’re talking about three, four, five or more prior lines of therapy you can get about 11 months with the Ide-cel.  

You could even get a longer remission off of all therapy if you move it earlier. Same with Cilta-cel. We had studies and different cohorts and you can be in a long remission. So, think of somebody who’s – myeloma’s incurable. It’s very treatable but it’s incurable for most. And so, you go from the expectation of staying on treatment until disease progression, much like other chronic conditions like diabetes. We don’t stop medicine for diabetes or high blood pressure.  

And it’s the same with myeloma and many of the cancers that we treat these days. And so, a CAR T-cell therapy will give patients the option of having that disease free interval where you can go and travel the world. I have patients that have bought RVs after their CAR T-cell therapy and now they’re going around the world – well, not the world. But around the United States.  

Katherine Banwell:

The country. 

Dr. Beth Faiman:

The country. And just really enjoying life and taking that time off and being realistic, knowing that we have to do bloodwork every month to make sure the myeloma’s still in remission because it can come back. But at least it’s sleeping for right now. So, you can go out and enjoy your life and take those trips and enjoy the little things and the big things.  

Katherine Banwell:

Yeah. Well, thank you for that advice. I’d like to get to a few audience questions that were sent in prior to the program. Alice asks, can you share more information about T-cell collection? A recent webinar mentioned that myeloma must be in good control. Can you share specifics about the bridging therapy prior to infusion?  

Dr. Beth Faiman:

Yes. So, again, the process is the lengthy process as we mentioned before. But for the actual T-cell collection, we will have approved you to get the therapy. Financially, we’ve cleared you. Socially, you’ve gotten your support systems and now we’re getting those cells out.  

We use a process called apheresis where a temporary catheter is placed under the skin, and it separates your white blood cells and then returns the red bloods and plasma back into the blood. And it sorts out those T cells. The process itself, you’re on the machine for anywhere for two or three hours. Hopefully, it’ll just be one day’s time. And then, they’ll manufacture those cells.  

So, during that period where we’ve put your cells and sent them away to wherever’s going to be doing the manufacturing, you’re going to need to get a treatment that’s going to keep you in remission from the myeloma. And it’s not going to prevent you from getting those cells safely back. So, we don’t want anything that’s too toxic for most people. So, what we’re doing now is we have that information that early on is better for myeloma to get these treatments. And so, the hope that bridging therapy won’t be as common of a thing anymore.  

Because now we’re selecting people that are – the myeloma’s just starting to act up. Let’s get those cells out, send them off, so we don’t have to do bridging therapy. We can just keep you – add a medication or take away another medication to keep you in remission. So, that’s the goal of bridging therapy. What’s that bridge to get your cells back in for some people? It might be a chemotherapy type of a thing. But for other people it’s just trying to get you that CAR T-cell collection and manufacturing so we don’t really have to change everything all up.  

And we’ve been very fortunate now that the wait lists have cleared in most institutions. CAR-T cell is available at more centers across the country and so we don’t have that backlog. And so, fortunately, bridging therapy will hopefully be a little bit less of a thing.  

Katherine Banwell:

We have another question. This one from Rita. What kind of monitoring takes places in the months following CAR T-cell therapy and what kinds of medicines are required afterward?  

Dr. Beth Faiman:

Oh, excellent. So, the monitoring is usually on the short-term, within the first 30 to 60 days afterwards, oftentimes depending on what your blood counts are showing. You might have to get blood counts tested more frequently. So, that complete blood count shows you the white cells, the red cells. The white cells fight infection. Red cells carry oxygen. Platelets clot the blood. That’s a marker of how well your bone marrow is functioning. It also can be – those innocent bystanders can go low temporarily after this procedure.  

So, definitely those CBCs need to be tested, for some people weekly and for some people every other week. And your healthcare team will tell you how often. After that first two to three months and your blood counts are all in good shape, then we can just go oftentimes to a monthly monitoring of the myeloma labs. So, that’s the CBC and the chemistry panel but also the paraproteins in the blood and the urine get monitored.  

There’s also another test called a CD4 count that’s something that you wouldn’t have had beforehand. The CD4 count is an immune count that we want to be over 200. Oftentimes,  you’ll be on an antibiotic called Bactrim or an inhaled called pentamidine to lessen the chance of a certain kind of infection called PJP, or pneumocystis. So, those are those atypical infections that we’re now seeing with CAR-T cell and other therapies.  

And as I mentioned, acyclovir to protect against shingles is a medication but you’re not going to be on any anti-myeloma medications other than maybe a bone strengthener if you get that intermittently. Fortunately, after CAR-T cell, you don’t have any anti myeloma therapy as long as you’re in remission.  

Katherine Banwell:

We also received this question from a viewer named Rob. If you receive CAR-T therapy, how long does it last and have you seen remission for a long time?  

Dr. Beth Faiman:

So, I’d like to tell Rob that I’ve seen a little bit of a remission and I’ve seen long-time remissions. Unfortunately, it goes back to the biology of the disease. People that have a more aggressive type of myeloma tend to not have as long of a remission but that’s not always the case. So, if you have what’s called a standard type of myeloma, which fortunately about 80 percent of the people have a standard or good type of myeloma, you can get an 11- to 24-month remission if you’ve had many prior therapies.  

Now, if we’re moving the CAR-T earlier lines of therapy, as in those two studies that I briefly mentioned with the Ide-cel and the Cilta-cel studies that are moving it to one to three prior lines of therapy, people are getting longer remissions.  

Unfortunately, I do not have a crystal ball. I can look at your disease genetics. I can look at how deep your remission status is and I can generally predict based on other studies how long of a remission you might get, but it’s not a guarantee. What works for one person might not work for the other so you take it with a grain of salt. We just say, “Gosh, this is a great therapy. We need to offer it to you while we have that window of opportunity. You’re in a good remission. We have a slot for you. We’re going to pick the best product for you. Let’s give you this option.” 

You might be one of those exceptional responders that are in remission for several years, which I do have people that have been in remission several years, fortunately.  

Katherine Banwell:

Okay. Well, thank you so much for the thoughtful responses to those questions. As we close out today’s program, can you talk about some of the ongoing research in CAR T-cell therapy and what you’re excited about?  

Dr. Beth Faiman:

Oh, my gosh. I am so excited about CAR T-cell therapy research. There are these what we call CRISPR gene edited technology, which is really personalizing the treatment in CAR-T.  

There’s what we call an off-the-shelf approach where we don’t have to manufacture one’s T cells to be a fighter. So, these CAR T-cell therapies are the kinds of clinical studies where if you are in a position where you want to hopefully get an earlier access to a great therapy, this CRISPR edited at – Caribou is what it’s called, that we have at my institution. That might be right for you.  

There’s also the different targets. For example, the Ide-cel and the Cilta-cel target what’s called BCMA or B-cell maturation antigen. Basically, the BCMA is expressed mostly on cancer cells and less so on healthy cells.  

And so, that’s what the target is for these current CAR-Ts. We have different targets. So, what does that mean for you? If you had a CAR T-cell therapy against BCMA or a bispecific against BCMA now we have these different targets so that gives you other options for remissions status. So, if you can, I am a big, strong advocate for clinical trials. Like I said, it’s getting better access. You have a healthcare team. There’s so much stigma associated with clinical trials, but every single person is a candidate for some sort of a trial or another.  

So, talk to your healthcare team or you can go to clinicaltrials.gov and then all the patient care organizations – International Myeloma Foundation, Multiple Myeloma Research Foundation, has access to clinical trial information as well for patients. So, yes, lots of good things. New targets. Off-the-shelf so you don’t have to manufacture. So, that represents new treatment options for many patients.  

Katherine Banwell:

Dr. Faiman, thank you so much for taking the time to join us today. 

Dr. Beth Faiman:

My pleasure. Thank you for having me.  

Katherine Banwell:

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

CAR T-Cell Therapy | Key Considerations for Myeloma Patients

CAR T-Cell Therapy | Key Considerations for Myeloma Patients from Patient Empowerment Network on Vimeo.

Myeloma expert and researcher Dr. Beth Faiman shares key considerations when planning for CAR T-cell therapy. Dr. Faiman reviews which patients qualify for CAR T-cell therapy, key aspects for patients to consider, and resources for clinical trials and CAR T-cell therapy information.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

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Planning for CAR T-Cell Therapy | Advice for Myeloma Patients

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Transcript:

Katherine Banwell:

I’m sure many of our viewers today are wondering who the therapy is right for, and when is it most appropriate in the course of myeloma? Could you address that?  

Dr. Beth Faiman:

Yeah, absolutely. So, currently, you have to have had three prior lines of therapy with drugs such as a CD38, which is – daratumumab (Darzalex) is a name of a medication.   

You have to have a drug such as lenalidomide (Revlimid) as well as a drug like bortezomib (Velcade). And you have to have had three lines of therapy. So, that’s how you can access the therapy. But if you’re willing to participate in a well-designed clinical trial there are studies with CAR T-cell therapy earlier on.  

So, one of the things that we’re advocating in the myeloma world is clinical trials. We haven’t gotten to where we are in 2024 with the advances in sciences, the advances in living longer and living well with myeloma, without the brave people before us that have participated in clinical trials.   

So, people who it’s right for would be if they qualify for a clinical trial before their third or fourth line of therapy or if they’ve had three or four prior lines of therapy.   

And there are other points to that which I’m sure we’ll talk about later on.  

Katherine Banwell:

In your opinion, what are three key considerations that myeloma patients and care partners should think about related to the CAR T-cell therapy approach?  

Dr. Beth Faiman:

Well, I would like to say that always when you’re selecting a therapy, think of the physical, the financial, and the social implications of that therapy. So, physically is the medication too strong for you? Are you too weak to take it? Or is it just right for you? So, finding the right medication for the right patient at the right dose at the right time. So, the physical component.

The financial component is also very important. So, maybe your insurance now won’t cover it but then there’s open enrollment in Medicare towards the end of the year or you can find financial support reimbursement through many of our generous organizations that will provide grants for certain medications.  

And then, the social. Do you have a care partner, as we discussed? The importance of being monitored for 30 days. If you don’t have a formal care partner, is there some system that we can help support you through so that you can have the different supports throughout. It’s not only that beginning part where you’re gaining the information – and I think of it like a timeline. The beginning part, you’re thinking about gathering information to the – in that process of getting yourselves back because of the side effects, which I think have been talked about in a prior webinar.  

And then, the post-monitoring where you go back to your community, taking antibiotics, antiviral medications, etc., to keep you living well longer. So, it’s a process.   

Katherine Banwell:

Well, it’s great advice, Dr. Faiman, thank you. I’d also like to add that if you’re considering CAR T-cell therapy, the Patient Empowerment Network has a wealth of information on this topic, including resource guides and interviews with experts like Dr. Faiman. And you can find those at powerfulpatients.org/myeloma.  

Planning for CAR T-Cell Therapy | Advice for Myeloma Patients

Planning for CAR T-Cell Therapy | Advice for Myeloma Patients from Patient Empowerment Network on Vimeo.

How can myeloma patients plan and prepare for CAR T-cell therapy? Myeloma expert and researcher Dr. Beth Faiman shares an overview of eligibility requirements, appointments to coordinate, multidisciplinary team members, and support resources to help in planning.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

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Transcript:

Katherine Banwell:

Can you give us an overview of the process and timeline for someone choosing CAR T-cell therapy for myeloma treatment?   

Dr. Beth Faiman:

Yes. So, CAR T-cell therapy, when we first started discussing this in the mid-2000s, I thought this was science fiction.  

Taking somebody’s own cells, engineering them to be fighters against the cancer cells. I thought it was science fiction. But now, we have two FDA-approved therapies for multiple myeloma. It’s Ide-cel, which was approved in 2021 and Cilta-cel, approved in 2022.  

Now, the process is lengthy, and I know you’ve covered this before but from my perspective, I think if you want to take something home form this webinar, plan early. So, you need to have three prior lines of therapy as a myeloma patient to qualify for this treatment. But you can start planning for it ahead of time.  

So, it’s not available in every center. So, you want to start researching what the closest center would be for you to have this therapy. Many different patient support networks will have these centers on their websites. So anyhow, you find out.  

“Okay. I want to learn more about a CAR T-cell therapy.” Then you have to meet with a specialist. So, you get that education, have that referral, and meet with a specialist at a center that does CAR T-cell therapy. And that might be where you got your initial transplant if you’ve then returned to the community. After that, then we find a slot for you when it’s ready. So, there is that process of financial, physical, social things that are checked in the background. You meet with a social worker, nurses, etc.  

Once you’ve confirmed that you’re going to go through this process – now, it might be three, six, nine months in the future, if you’re a planner – but if you want to just gain information, it’s that harvesting and storing of the cells. That’s where I try to tell people age is not a number. You can be at any age and you qualify for this therapy. We’ve had people well into their late 70s to early 80s who have gotten these therapies. Long story short, it’s a process.  

You get your cells harvested and then while they’re being manufactured into fighters, they take the T cells from your blood through an apheresis machine and freeze them, send them off, make them into fighters, and then reinfuse them in your bloodstream. It’s a long process. It can take anywhere from two to three months from when you decide it’s right for you.  

Katherine Banwell:

Well, thank you for explaining that. That’s really important. It puts into perspective. It’s a big undertaking. But also, quite manageable, I think, right, with the right team and support. Who are the members?  

Dr. Beth Faiman:

Absolutely. The family members, friends, and, of course – I like to use the words the multidisciplinary team. That’s your physicians, your social workers, nurses, nurse practitioners like me, pharmacists, and then all your other specialists.  

So really, mounting that team from diagnosis and throughout your whole journey as a myeloma patient can really enrichen your life and help you thrive in that environment.  

Katherine Banwell:

Yeah. It sounds like there’s a lot of support for someone going through this process and that the care partner also plays a critical role on the care team, right?  

Dr. Beth Faiman:

Oh, absolutely. So, I am a big advocate for care partner though not everybody has a caregiver. So, it can be a formal caregiver, somebody’s spouse, daughter, son, significant other. Or it can be an informal caregiver. So, I’ve had patients that – because you need to have a care partner to qualify for CAR T-cell therapy, because patients need to be monitored for about 30 days afterwards. So, that might be pulling in friends from your place of worship, people from the community, and then also people from the cancer center.  

Some of the larger centers that do the CART-cell therapy have a network setup where you get this list of people that have volunteered to drive you to appointments or maybe arrange for Uber help to drive you back and forth. I am not plugging Uber or Lyft, but a rideshare company.

And so, finding out those resources can help anyone – just about anyone – access these CAR  T-cell therapies, because you can have a long-term remission. Think about somebody who’s been through treatment A, B, C, or D and then now, “Gosh, maybe my life is going to be shortened.”  

Not necessarily. If this is the right recipe to control their myeloma then they can get 11, 24 months off of everything – just antibiotics – and be monitored. And so, it puts them at a position where if you can get the care partner, get a care team, to support you then you can have access to a potentially life extending with good quality of life therapy.   

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale from Patient Empowerment Network on Vimeo.

What concerns do myeloma patients need to know about CAR T-cell therapy? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains patient qualification for CAR T-cell therapy, including the number and type of prior therapies.

Download Guide  |  Descargar Guía

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Transcript:

Lisa Hatfield:

So we have another patient asking, “Do myeloma patients require multiple prior therapies prior to being eligible for CAR T?” And what’s the rationale for not implementing CAR T immediately, which probably has to do with FDA approval based on clinical trials at this point?

Dr. Sikander Ailawadhi:

So any drug, let alone CAR T, any drug can only be given in the situation that it is approved by the FDA. So basically in accordance with that drug’s FDA approval label. Currently, CAR T-cell therapy is approved in the U.S. after at least four prior lines of therapy. And the patient must have had treatment with at least one proteasome inhibitor, for which we have three drugs, bortezomib (Velcade), ixazomib (Ninlaro), and carfilzomib. They must have been treated with at least one prior immunomodulatory drug; lenalidomide (Revlimid), thalidomide (Thalomid), pomalidomide.

And they must have been previously treated by at least one monoclonal antibody, daratumumab (Darzalex) or Isatuximab (Sarclisa). Once the patient has had all these criteria met, they’ve become a candidate for CAR T-cell therapy. Frankly, we cannot just use a drug anywhere because we cannot use a drug where it has not shown to be of benefit. And importantly, it has not shown to be of any risk. So CAR T-cell therapy in the first line setting is being studied in clinical trials, but is not FDA-approved. Currently approved only after four prior lines, but the FDA is reviewing data for both the CAR Ts to see if they may be available sooner. As of right now, that approval is still pending.

Lisa Hatfield:

Okay, thank you. We’re hopeful that that will happen soon.

Dr. Sikander Ailawadhi:

Hopeful.

Lisa Hatfield:

Yeah. So an interesting question from a patient, “Does CAR-T therapy actually change one’s DNA?”

Dr. Sikander Ailawadhi:

No. The CAR T therapy does not change one’s DNA. What happens is, there are T cells taken out of a patient. The DNA of those T cells is modified and then those T cells are given back to the patient. Those T cells do not go and integrate into your other healthy body cells or your stem cells, et cetera. Those T cells, it’s almost like giving a boost of immunity, which is targeted against your myeloma. So those T cells go in and they fill those myeloma cells.

Now we hope that those T cells perpetuate and teach or create some memory T cells and that immunity lasts a little bit longer. But all of that genetic modification stays within the T cells. It does not integrate anywhere else. Now, I know there was a previous question about T-cell lymphomas, that is related to this question in a way because the risk that is theoretical is, that that genetic modification in the T cells might make those T cells replicate uncontrollably leading to a T-cell cancer or T-cell lymphoma. But I’m saying that this is theoretical because while it is possible, it happens extremely rarely and even in the cases where the cancer happened, it has  been seen that the cancer may not come from that portion of the DNA that was…that’s where the modification was done. So, low risk.


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