Cevostamab Post-CAR T-Cell Therapy is Safe in Heavily Pretreated Multiple Myeloma

Adverse effects were manageable when patients with heavily pretreated multiple myeloma were given cevostamab consolidation after receiving CAR T-cell therapy.

For patients with heavily pretreated multiple myeloma, fixed-duration cevostamab consolidation after BCMA CAR T-cell therapy was feasible and safe, according to results from the phase 2 STEM trial (NCT05801939) presented at the 22^nd International Myeloma Society Annual Meeting.

Pre-cevostamab, the complete response (CR) rate was 63%; it was 81% when given CD81, 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,” said Adam D. Cohen, MD, director of Myeloma Immunotherapy and associate professor of medicine at the Hospital of the University of Pennsylvania, 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 (CRS) 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 cut-off 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 del17p; 59% had gain or amp 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 were 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 non-hematologic 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, 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 the 22^nd International Myeloma Society Annual Meeting; September 17-20, 2025, Toronto, Canada. Abstract OA-67.