Cevostamab Delivers on Antitumor Activity in Multiple Myeloma

The bispecific T-cell engager antibody cevostamab delivered feasible and well-tolerated antitumor activities after treatment with BCMA-directed chimeric antigen receptor (CAR) T-cell therapy in patients with heavily pretreated multiple myeloma, according to data from the phase 2 STEM trial (NCT05801939) presented at the 22nd International Myeloma Society Annual Meeting and Exposition.¹

Prior to administration of cevostamab, the complete response (CR) rate was 63% and 93% at 1 year post CAR T-cell therapy. The 1-year minimal residual disease (MRD)–negative CR rate was 93%. Regarding progression-free survival and overall survival, the median follow-up was 12 months, but “the vast majority of patients are alive and remain progression-free,” Adam D. Cohen, MD, director of myeloma immunotherapy and associate professor of medicine at the Hospital of the University of Pennsylvania, said during the presentation.

Patients were given idecabtagene vicleucel (ide-cel; Abecma) or ciltacabtagene autoleucel (cilta-cel; Carvykti) as standard of care, then, at 10 to 12 weeks post treatment, enrolled in the STEM trial. Cevostamab was given intravenously at 3.6 mg on cycle 1 day 1 and 132 mg on cycle 1 day 8 and, thereafter, every 3 weeks for 8 cycles. On both infusion days, patients were required to be hospitalized for 48 hours. Patients were then assessed for an MRD-negative CR. If they achieved it, they were observed; if they did not, they went back to treatment with cevostamab every 3 weeks for 8 cycles.

The primary end point was the MRD-negative CR rate at 12 months post CAR T-cell therapy.

Patients were eligible for treatment if they had relapsed/refractory multiple myeloma; received commercial CAR T-cell therapy between 6 and 10 weeks prior to enrollment; had 4 or more prior lines of treatment, including an immunomodulatory drug, proteasome inhibitor, and CD38 antibody; and had stable disease or better after CAR T-cell therapy. Patients were excluded if they had progressive disease post CAR T-cell therapy, prior cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome of grade 3 or higher, or prior Parkinsonism.

A total of 27 patients were treated. The interim analysis cutoff date was June 27, 2025.

The median patient age was 64 years, 74% of patients were male, and 78% were White. The median time from diagnosis to study participation was 4.6 years. Extramedullary disease was noted in 19% of patients. Cytogenetics included 44% of patients having t(4;14), t(14;16), or del(17p); 59% had gain or amplification of 1q; 22% had del(1p). Also, 74% had at least 1 of the listed, and 41% had at least 2 of the listed.

A total of 93% of patients received cilta-cel, and 7% had ide-cel. The median number of prior lines of CAR T-cell therapy was 4. Additionally, 74% of patients had disease that was triple-class refractory.

Hematologic adverse effects (AEs) of any grade and grade 3/4, respectively, included lymphopenia (74% vs 67%), neutropenia (74% vs 44%), thrombocytopenia (41% vs 22%), anemia (26% vs 0%), and febrile neutropenia (4% vs 4%). Any-grade and grade 3/4 nonhematologic AEs included infections (52% vs 15%), cytokine release syndrome (15% vs 0%), cough (59% vs 0%), rash (44% vs 0%), and upper respiratory infection (37% vs 0%).

A total of 4 patients experienced unusual immune-related AEs such as grade 2 enterocolitis in cycle 4, grade 3 ataxia/gait disturbance/peripheral neuropathy in cycle 8, grade 3 transaminitis and grade 1 autoimmune hepatitis in cycle 1, and grade 4 immune thrombocytopenia in cycle 8. Prior to any AEs, 3 of the 4 patients had a preceding infection. All unusual immune-related AEs were resolved.

“To date, over 90% of evaluable patients [are] sustaining MRD-negative CR at 1 year post CAR T. Enrollment [in the trial] is complete; treatment and follow-up are ongoing,” Cohen concluded.

_REFERENCE:

_{Cohen AD. Phase 2 study of cevostamab consolidation following BCMA CAR T cell therapy: preliminary safety and efficacy data from the “STEM” (sequential T cell-engagement for myeloma) trial. Presented at: 22nd International Myeloma Society Annual Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract OA-67.}