Cevostamab Shows Promising Results as Post-CAR T Consolidation in Relapsed/Refractory Multiple Myeloma

A new study shows that cevostemab (Genentech) offers potential promise to patients with relapsed/refractory multiple myeloma (RRMM), researchers said at the 2025 International Myeloma Society Annual Meeting.

BCMA-targeted chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for relapsed/refractory multiple myeloma (RRMM), demonstrating unprecedented response rates. However, relapse remains a significant challenge, highlighting the need for strategies to deepen and sustain responses. FcRH5, an antigen expressed independently of BCMA, represents a potential complementary target. New data point to cevostamab (Genentech), an FcRH5-directed T cell-engaging bispecific antibody, as a post-CAR T consolidation.¹

Cevostamab demonstrates promising activity in RRMM, including in patients previously treated with BCMA-targeted therapies. Investigators hypothesized that administering fixed-duration cevostamab following CAR T-cell therapy would be feasible, tolerable, and enhance sustained minimal residual disease (MRD)-negative complete response (CR) rates. An ongoing single-institution, investigator-initiated study (NCT05801939) is evaluating this approach.^1,2

Eligible patients with RRMM with stable disease or better received cevostamab 10 to 12 weeks following standard of care CAR T-cell therapies including idecabtagene vicleucel (ide-cel, Abecma; Celgene Corporation/Bristol Myers Squibb) and ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech, Inc/Legend Biotech). The regimen began with a step-up dose of 3.6 mg intravenously (IV) on cycle 1 day 1, followed by 132 mg starting on cycle 1 day 8 and continuing every 3 weeks for a total of 8 cycles.¹

Patients who achieved MRD-negative CR after 8 cycles discontinued therapy and are observed. Those without MRD-negative CR received an additional 8 cycles. MRD was assessed using Adaptive Clonoseq with a sensitivity of 10^–5, and all patients receive prophylactic intravenous immunoglobulin. The primary end point is the frequency of MRD-negative CR 1-year post-CAR T therapy.¹

As of June 27, 2025, 27 patients (median age 64; 20 men, 7 women) were enrolled. Most patients (74%) had high-risk cytogenetics, with 41% presenting 2 or more high-risk features, and 19% had extramedullary disease. The median number of prior therapy lines was 4, with 74% being triple-class refractory. Notably, 11% had prior BCMA-directed therapy, and 11% had received talquetamab (Talvey; Janssen Biotech). Responses at enrollment included 63% CR/stringent CR (sCR), 15% very good partial response (VGPR), 18% partial response (PR), and 4% stable disease (SD).¹

Cevostamab consolidation was generally well-tolerated. No dose-limiting toxicities were observed, and there were no cases of immune effector cell-associated toxicity syndrome (ICANS) or hemophagocytic lymphohistiocytosis. Cytokine release syndrome occurred in 4 patients (15%; 3 grade 1, 1 grade 2), and infusion reactions were reported in 19% (all grade 1/2). Hematologic toxicities included lymphopenia (74%, grade 3/4 67%), neutropenia (74%, grade 3/4 44%), thrombocytopenia (41%, grade 3/4 22%), and mild liver enzyme elevations. Infections occurred in 52% of patients, with grade 3/4 in 15%.¹

The preliminary efficacy is encouraging. Among 22 patients evaluable after 8 cycles, 81% achieved sCR, 95% were MRD-negative at 10^–5, and 91% at 10^–6 sensitivity. At 1-year post-CAR T therapy, 93% of 14 evaluable patients maintained MRD-negative sCR at 10^–5 and 79% at 10^–6. With a median follow-up of 12 months, estimated 12-month progression-free and overall survival rates were both 95%.¹

These early results suggest that cevostamab consolidation following CAR T-cell therapy is feasible, well-tolerated, and capable of producing durable MRD-negative responses in late-line RRMM, offering a promising approach to improve long-term outcomes for this challenging patient population.

REFERENCES

1. Cohen A, Susanibar-Adaniya S, Garfall A, et al. 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: 2025 International Myeloma Society Annual Meeting. Toronto, Canada. Abstract OA-67

2. Cevostamab following CAR T cell therapy for RRMM. Clinicaltrials.gov. Updated October 1, 2024. Accessed September 24, 2025. https://clinicaltrials.gov/study/NCT05801939