Novel BCMA-Targeting Agents for the Treatment of Relapsed/Refractory Multiple Myeloma

A panel of doctors discuss the available treatment options for early and late relapsed multiple myeloma, including approved novel BCMA-targeting agents.

Rafael Fonseca, MD: In our next session, we’re going to discuss expanding our armamentarium for the treatment of myeloma with novel therapies. We recently had the second CAR [chimeric antigen receptor] T-cell therapy approved for the treatment of multiple myeloma. There has been a thought of a growing complexity with all these options. At the same time, some of the studies converge into some clear messages. Let’s talk about what we know and what we saw at ASH [American Society of Hematology annual meeting].

A key concept is that we’re now all thinking early relapse, perhaps particularly even the first relapse, and then later relapses. Things will change, of course. A year or two from now, our conversation will be different because we know there’s going to be a forward march by all these T-cell engagers, the bispecifics, and CAR T cells. But let’s talk about what we know today, early relapse vs late relapse. Jeff, maybe you can start with a little overview of the BCMA-targeting agents that are either approved or in development for the treatment of myeloma.

Jeff Matous, MD: We have 3 approved. One is belantamab mafodotin, the antibody-drug conjugate targeting BCMA. We have 2 approved CAR T-cell products, ide-cel [idecabtagene vicleucel] and cilta-cel [ciltacabtagene autoleucel], out there as well. Those are our approved agents. I’ve seen in our practice and community that belantamab has primarily been used when doctors are pretty desperate. They’ve been saving it for when their patients have had several lines of therapy and they’re looking for something else to do. Belantamab has found a niche there, although it’s being studied in a lot of the DREAMM trials in various and sundry combinations.

The CAR T-cell products that are FDA approved are very exciting, but they’re in short supply, where we’re not going to be able to treat as many patients as we’d like as these products roll out. A lot of the BCMA targets that we have are available through clinical trials. At our center, we have NK [natural killer] cell, BCMA-targeting agents. We have 3 of the BCMA-targeting, T-cell–redirecting antibodies. There are also BCMA CARs, both autologous and allogeneic. All of these are being explored across the spectrum. BCMA is a hot target for a lot of our novel therapies in myeloma, and they’re looking exciting. We’re super excited to be able to offer these to our patients. We have no trouble finding patients to enroll on these trials.

Rafael Fonseca, MD: No question. Dr Patel, we saw an update on the MajesTEC-1 study with teclistamab, a BCMA-targeting bispecific. What were your takeaways from that presentation?

Krina Patel, MD: With the bispecifics, we’re getting more of the longer-term results now, and they’re doing really well after those CAR Ts. Conflict of interest, I’m a CAR T girl, but I’m definitely impressed by the bispecifics. They’re all a little different, but these were in relapsed/refractory patients, and this is a subcutaneous version, which is very patient-friendly, as we’ve learned from the daratumumab story, so I like that. The dosing is 1500 μg/kg weekly, and there’s a step up. They started with 60 μg/kg and then 300 μg/kg to decrease the CRS [cytokine release syndrome] rate. They presented the phase 2 portion of their study with almost 160 patients. These patients were relapsed/refractory, with about 5 lines of therapy. There was a patient with 15 lines. Seventy-seven percent were triple-class refractory, and about 30% were penta-refractory, so patients had seen these drugs and relapsed on them.

The nice thing is that they didn’t see a lot of new safety issues compared with their phase 1. It was about 67% CRS, but 99% of those were grade 1/2, so very easy to treat. One patient had grade 3 that resolved. And it happens early. This matters in terms of treatment. Usually it happens within 2 days, and then it lasts for 2 days, and then the CRS goes away. They saw some ICANS [immune effector cell-associated neurotoxicity syndrome], but it was about 2% and was all grade 1/2 that all resolved. There were no major neurotoxicity issues, which we sometimes see in these different products.

They saw grade 3/4 neutropenia in 45%, and thrombocytopenia in 18%. Overall, the response rates were about 65%, with 40% being CR [complete response] or better. These have been deepening as time goes on. The 6-month duration of response was 90%. They had 1 patient who was over 15 or 18 months on their swimmer plot who’s still responding to their treatment. These are pretty phenomenal responses. The duration of response will be interesting to see as we continue following their updates.

Rafael Fonseca, MD: Thank you. We’re very fortunate, because even though we’re talking about BCMA, there are other targets.

Transcript edited for clarity.

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