Behind the FDA Approvals of BCMA-Directed Therapies for Multiple Myeloma

Adam Cohen, MD, director, Myeloma Immunotherapy, and associate professor of Medicine at the Hospital of the University of Pennsylvania, discusses the current FDA-approved BCMA-directed therapies in the multiple myeloma space and the clinical data supporting each agent.

Since 2020, the FDA has granted approvals to belantamab mafodotin (BLENREP), ciltacabtaene autoleucel (cilta-cel; Carvykti), and idecabtagene vicleucel (ide-cel; Abecma), for patients with multiple myeloma.

These approvals were based on data from the phase 2 DREAMM-2 study (NCT03525678), phase 2 KarMMa study (NCT03361748), and phase 1b/2 CARTITUDE-1 study (NCT03548207).

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0:08 | The first BCMA-targeted drug that was approved was called belantamab mafodotin. This is an anti-BCMA antibody drug conjugate. It's a monoclonal antibody that has a microtubule poison on the end of it called MMAF, and it's given as an IV infusion every 3 weeks. It was approved based on the DREAMM-2 study which looked at 2 different doses of the drug and found that the 2.5 mg/kg dose was sort of the optimal one going forward, and that's the one that got approved.

0:38 | The response rate in that heavily refractory population of a median 6-7 prior lines of therapy was around 32%. Median [progression-free survival] PFS was only about 3 months, but the median duration of response was 11 months, meaning if you did get a response, those responses tended to be fairly durable. We've had patients on this drug going on more than 2 and a half years. So that's the first one that got approved in 2020.

1:06 | The next that was approved was ide-cel, which is a CAR T-cell product targeting BCMA, which was approved in the summer of 2021. This was based on the KarMMa study, which was a multi-institution, single-arm, phase 2 study giving these BCMA-targeted CAR T cells to patients with heavily refractory myeloma. In that study, the overall response rate was 73%, with almost 40% of patients getting a CR [complete response]. The median progression-free survival for all patients was around 9 months, but in the group that got the highest dose of 450 million cells, which is the target dose approved by the FDA, median PFS was close to 12 months. This was unprecedented activity in this heavily pretreated population of patients.

1:57 | The final product, that just got approved at the end of February 2022, is cilta-cel. This is another CAR T-cell product targeting BCMA. It has a distinct CAR construct compared with ide-cel and was also tested in a multi-institution, phase 2 study in the United States called CARTITUDE-1. In this study with 97 patients, the overall response rate was 98% with over 80% of patients achieving a complete remission. Median progression-free survival has not yet been reached with about 2 years of follow up. There are remarkable response rates, depth of response, and PFS with these CAR T-cell products in particular. I think that's what's generating a lot of excitement in the field right now, and now we have 2 different CAR products that are approved and available for our patients, which is great.