Additional Advances in Multiple Myeloma Research and Clinical Trials With Rahul Banerjee, MD, FACP

Dr. Rahul Banerjee, Assistant Professor in the Division of Medical Oncology at the University of Washington, Fred Hutchinson Cancer Center, is currently serving as chair of i3 Health’s online activity and fellows meeting series, Leveraging BCMA-Directed Therapies for Improved Patient Outcomes in Relapsed/Refractory Multiple Myeloma. Since recording the activity, numerous updates have occurred in research for this field, with the most notable being the recent expanded approvals of idecabtagene vicleucel and ciltacabtagene autoleucel for earlier lines of therapy. In this interview, Dr. Banerjee shares additional insight into these expanded approvals and how they affect the treatment landscape for patients with multiple myeloma.

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Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, I’m joined by our Editor in Chief, Dr. Rahul Banerjee, who is also currently serving as chair of i3 Health’s online activity and fellows meeting series, Leveraging BCMA-Directed Therapies For Improved Patient Outcomes in Relapsed/Refractory Multiple Myeloma.

Since recording this activity, numerous updates have occurred in research for this field, including the recent expanded approvals of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Today, Dr. Banerjee is sharing some more insight into these expanded approvals in how they affect the treatment landscape for patients with multiple myeloma. Dr. Banerjee, always a pleasure to speak with you.

Rahul Banerjee, MD, FACP: Thank you, Keira, and thank you to everyone for listening in. This is one of those full-court press moments where I’m actually covering our inpatient service right now, but filming this to talk about how idecabtagene vicleucel and ciltacabtagene autoleucel—two BCMA-directed chimeric receptor antigen (CAR) T therapies for multiple myeloma—have been approved for earlier lines. There are some nuances in terms of what drugs patients have to have been exposed to, but in general, cilta-cel is for one prior line and ide-cel is for two prior lines.

This is a seismic change in the field. I cannot understate the importance of that. Prior to this, both CAR T products, which were approved in the last five years, were only approved for patients who’d had four prior lines of therapy. Interestingly, the KarMMa-1 trial did three prior lines of therapy. However, the approval was for four prior lines of therapy, and that was tricky.

There were a couple of studies showing that only a minority of patients would actually become eligible for these particular therapies. There was another study showing that for patients who were on the wait list, for example, especially early on, patients were more likely to die than they were to actually get CAR T therapy. This is partly because when someone gets to four prior lines of therapy, it’s a tricky spot to be in. Their disease often is more aggressive, more difficult to manage. They often have more side effects from the previous therapies that they’ve been on.

Remember that CAR T is typically about a two-to-three–month footprint of a patient’s life that’s taken up for the collection, the manufacturing period with bridging in between, the actual CAR T infusion, and then the actual monitoring period thereafter. It’s often hard to maintain disease control during those times for these patients. I was very guilty of this—I would argue doing the right thing for my patients, but honestly, fourth-line therapy did not work that well in myeloma—so as soon as someone got to three prior lines, we’re just kind of checking off a box saying, “What can we call a fourth line of therapy?” We’re just doing this to check off this box and get them onto the on-label indication for this therapy.

It didn’t quite make sense, especially because physicians like myself don’t really think in terms of lines of therapy. Lines of therapy are confusing to count and very nuanced in terms of what is a line of therapy, what’s the change in an existing line, what’s a new line, etc.  These new approvals put that kind of decision making to move CAR T in the earlier lines into our hands. I’m not saying that everybody needs CAR T as second- or third-line therapy. Actually, as I’ll get to, I would say the reverse. I would not say that. But there are some patients who absolutely need CAR T in second-line or third-line therapy. I’m glad that it’s now something that’s within my jurisdiction to discuss with the patients—”Here are your options with conventional therapies, CAR T therapy, and so forth.” I think that’s remarkable.

There are patients who definitely stand to lose with our previous CAR T approvals. Typically, patients with functional high-risk disease—early relapse after the first line of therapy, patients who had very limited treatment options, refractory disease to their prior lines of therapy, and so forth—those are the patients for whom getting them four prior lines was very difficult. Now, I have CAR T as a tool to use for them earlier.

People have asked me—patients, physicians, even my colleagues—”Does this mean that everybody should be getting CAR T as second-line therapy?” The answer is there is clearly no. I can think of three distinct reasons why that might be the case. One, standard therapies do work very well for some of our patients. For example, for the patient who’s had many years of remission after transplant, after frontline therapy, and is doing pretty well, I think a CD38 plus carfilzomib/dexamethasone (Kd)strategy, for example, like isatuximab-Kd or daratumumab-Kd, may work very well for them.

Two, I think that CAR T therapy does have its side effects. It’s not a totally benign treatment option, and better CAR T options are on the way. But for some patients, they may be worried and say, “Look, I’m worried about this risk of cytopenias. I’m worried about what neurotoxicity might mean for me. I’m worried about delayed rare toxicities, for example, Parkinsonism symptoms.” Now there’s a box warning about second malignancies that we discuss with our patients. So, CAR T is not for everybody in that regard.

Thirdly, it’s worth noting that even with the new approvals, it doesn’t change where CAR T is available. It’s only available at large, high-volume centers, typically at academic centers. Most of our patients don’t live with an easy driving distance of there. If a patient with indolent disease and biochemical relapse is trying to decide between, “Well, should I uproot my life and move to the big city for three months for CAR T therapy, or should I just keep doing what I’m doing with my local oncologists whom I know the best and wait, and then at subsequent relapse, get the best CAR T therapy available in 2028?” I’d say choose the latter. Do what makes the most sense for you.

So, I think these approvals are excellent because, again, they give us more options. Neither the FDA nor any of us are saying it’s a requirement to do CAR T as second-line or third-line therapy, but it’s an option. And for the appropriate patient, it’s absolutely the right option for them.

Oncology Data Advisor: Awesome. Well, thank you so much for coming on today to give us this really insightful perspective about the two new approvals. To everyone listening, be sure to visit i3health.com to view Dr. Banerjee’s full presentation on BCMA-directed therapies and claim free CME credit. Thanks again.

Transcript edited for clarity. Any views expressed above are the speakers’ own and do not necessarily reflect those of Oncology Data Advisor.

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