Bispecific Antibodies vs CAR T-Cell Therapy in Multiple Myeloma

Video

An expert panel compares bispecific antibodies with CAR T-cell therapy and discusses treatment sequencing.

Transcript:

Ola Landgren, MD, PhD: What about CAR [chimeric antigen receptor] T cells and bispecifics? Is there a sequence, Dickran? Which should go first? Does it have to be one or the other? Can you go from one to the other, or from the other to the first? How does that work?

Dickran Kazandjian, MD: CAR T cells and bispecific antibodies are 2 different types of drugs that work similarly in the body. There are pluses and minuses for each of them. I don’t want to go into all the details, but what I like about bispecific antibodies is [that] sometimes you can’t always foresee when it’s time to start a patient on that therapy, and sometimes you just don’t have the time to plan for it. Bispecifics, as they say…[are] off-the-shelf and easier to give. In those patients, another major difference is [that], as far as what we can tell now, even though we’re not supposed to compare studies [with] studies, it does seem like on average CAR T therapies have a risk of higher-grade cytokine release syndrome and [immune effector cell-associated neurotoxicity] compared with bispecific antibodies. [For example], if you have a more frail patient, you probably ought to use bispecifics over CAR T. In my mind, the biggest advantage of CAR T is it’s a 1-time deal, so you get 1 shot and then a patient could go into remission for a long time without any therapy. That’s the nice thing about that, if it works.

Ola Landgren, MD, PhD: Ben, in your practice, do you counsel patients to always do CAR T cells first and then do bispecifics? Or do you counsel them to always do bispecifics first? Or do you tell them that either way is OK? What is your take on that?

Benjamin Diamond, MD: In a perfect world, we’d have [all these options] available to all of us all the time. But that’s often not the case, unfortunately. We do have some data that show that you can get one agent and then get the next and still have responses. We’ve seen that with elranatamab, and we’ve certainly seen that with some of the other bispecific antibodies, so we know that’s an option…. When patients are on their third or fourth line and you see things aren’t going great, you can put them on the wait-list for CAR T, but you always have the bispecific antibodies in your back pocket, ready to go.

Ola Landgren, MD, PhD: Do you have to build in a little time window with some other therapy in between? Or can you go from, say, a BCMA [B-cell maturation antigen]-targeted bispecific? And if that unfortunately turns into relapse disease, can you go right to the CAR T cell with BCMA? Or do we need to do some other therapy in between?

Benjamin Diamond, MD: I’m glad you brought it up. Certainly, we don’t have a ton of data to help us guide this decision, but in practice, we’re seeing that if you can stagger the therapies and perhaps use a therapy with a different mechanism of action—again, another great place for a trial—you might have better luck with a response if you’re not sequencing 2 BCMA-directed therapies back-to-back.

Ola Landgren, MD, PhD: Do you have anything else to add to this conversation, Dennis? Bispecifics, CAR T cells, patients—what are they asking for? Are they all coming to ask for CAR T cells, or do they all come for bispecifics, or both?

Dennis Verducci, APRN: It’s a good question. It depends on the patient. In our clinic, we’ve had patients who have had myeloma for 10-plus years with multiple relapses, and now they’re at a point where they’re BCMA-targeted naïve. For those patients, it may make sense to do 1 and done, as Dickran said. Whereas, if they go to a bispecific, it’s still more trips to the infusion center weekly. So for those types of patients, CAR T cell would probably make the most sense.

Ola Landgren, MD, PhD: There are some recent data communicated from real-world experience with these therapies [that show] shorter duration. Dickran, what is your take on that?

Dickran Kazandjian, MD: Shorter duration in terms of [what]?

Ola Landgren, MD, PhD: Shorter duration of benefit, that the progression-free survival is shorter than what the trials show.

Dickran Kazandjian, MD: I’m not surprised. I think the same thing happens [with many drugs]. But I think about clinical trials; it takes a certain kind of patient to get on a clinical trial. Then when you’ve put it out in the community, it’s sometimes a little more difficult in terms of the patients you get on trials and the outcomes.

Ola Landgren, MD, PhD: I think what you’re saying is it’s very important to emphasize that it’s not unique to these particular drugs. Once trials have been completed, people like us have access to them but certain groups of patients—say, patients with plasma cell leukemia, or patients with very low platelet counts, or many other factors—are excluded from the trials. When we have those patients in our clinics, maybe we give these patients a lot of platelets so they go over the threshold. Or if they have plasma cell leukemia, we discuss that with the patients and say, “We unfortunately don’t have many other good options, so we would be willing to consider this.” This would not be a contraindication, but the patients are not eligible for a trial, so they are sicker patients. I think this happens all the time with many drugs, if not all drugs. That’s what you’re saying?

Dickran Kazandjian, MD: Yes, that happens with all studies and all drugs. Absolutely.

Ola Landgren, MD, PhD: It’s almost like when you get your first driver’s license, that’s when you really can start learning how to drive a car. That’s how it is with drug approvals. The drugs get approved, then we can really figure out how to use them.

Transcript edited for clarity.

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