Pre-Cevostamab Treatment May Not Impact Outcomes as Much in Multiple Myeloma

Adam Cohen, MD, discussed the reasoning behind most patients in the phase 2 STEM trial (NCT05801939) having received 4 or more lines of prior treatment, and how these outcomes may have impacted the use of cevostamab. The STEM trial, presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, was designed to assess cevostamab consolidation after BCMA CAR T-cell therapy for patients with multiple myeloma.

The study was initially launched in 2023, with an interim analysis data cutoff of June 27, 2025. In 2023, Cohen explained that the FDA labeled CAR T-cell therapy products for use only after 4 or more lines of therapy. Now, the approval stands at 1 to 3 prior lines.

Cohen, director of Myeloma Immunotherapy and associate professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania, believes that because patients have received fewer prior therapies, the outcomes from treatment will be better, and he describes their bone marrow as less “beaten up”.

Transcript:

The study was originally designed in 2023 when CAR T cells were only approved after 4 or more prior lines. Those were the patients who were getting on the study, because all patients were getting commercial CAR T-cells. That was amended in 2024 when the label changed, and we could give [CAR T-cell therapy] a little earlier, but in the end, this was a heavily pretreated group. What I think that means is, biologically, these patients probably have worse disease. They’ve seen more treatments. They all were triple class exposed to [proteasome inhibitors, immunomodulatory agents], and CD38 [treatments], and three-quarters [of patients] were refractory. It means it’s a tougher group of patients to treat. With more lines of therapy, their bone marrows are beaten up a little more, and that might explain some of the cytopenias that we were seeing. Even though patients had to have some count recovery post-CAR T to get on the trial, their bone marrow may have been a little bit more at risk. Now that we’re using CAR T-cells earlier and they’re approved in 1 to 3 prior lines, the patients might not be beaten up as much. They may have less resistant disease. They may have healthier T-cells. It might work even better in that setting. That’s what we’re hoping to see. If we do a follow-up study, the median prior lines will probably be fewer, and it’ll be interesting to see what happens.

Reference

Cohen A, Susanibar-Adaniya S, Garfall A, et al. Phase 2 study of cevostamab consolidation following BCMA CAR T cell therapy: preliminary safety, efficacy, and correlative data from the “STEM” (Sequential T Cell-Engagement for Myeloma) trial. Blood. 2025;146(suppl 1):699. doi.10.1182/blood-2025-699