Cevostamab: A New Strategy to Extend the Promise of CAR T-cell Therapy in Multiple Myeloma
A remarkable 95% progression-free survival rate at 12 months – that’s the early signal emerging from a phase 2 study evaluating cevostamab consolidation following CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM). Presented at the 2025 International Myeloma Society Annual Meeting, these findings suggest a powerful new approach to overcome the persistent challenge of relapse and deepen responses in a patient population with limited options. While CAR T-cell therapies like idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized RRMM treatment, the durability of those responses remains a critical area of focus.
Beyond BCMA: Targeting FcRH5 for Lasting Remission
The key to this promising strategy lies in targeting FcRH5, a protein expressed on myeloma cells independently of the more commonly targeted BCMA. This distinction is crucial. Many patients eventually relapse after CAR T-cell therapy due to BCMA antigen loss. Cevostamab, a T-cell engaging bispecific antibody directed against FcRH5, offers a complementary mechanism of action, potentially circumventing this resistance pathway. The ongoing “STEM” trial (NCT05801939) is evaluating whether administering fixed-duration cevostamab after CAR T-cell infusion can solidify remissions and prevent relapse.
Study Details and Patient Characteristics
The study enrolled 27 heavily pre-treated patients with RRMM who had received prior CAR T-cell therapy. A significant proportion (74%) were considered high-risk based on cytogenetic abnormalities, and the median patient had received four prior lines of therapy. Notably, a subset had already been exposed to BCMA-directed therapies and even the newer talquetamab, highlighting the advanced stage of disease in this cohort. Patients received cevostamab intravenously for up to 16 cycles, with treatment continuing until achieving minimal residual disease (MRD)-negative complete response (CR) or disease progression.
Safety and Tolerability: A Manageable Profile
Importantly, cevostamab consolidation demonstrated a manageable safety profile. No dose-limiting toxicities or severe immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. While cytokine release syndrome (CRS) occurred in 15% of patients and infusion reactions in 19%, these were generally mild (Grade 1 or 2). Hematologic toxicities, including lymphopenia, neutropenia, and thrombocytopenia, were common, but largely manageable with supportive care. Infections occurred in over half the patients, with Grade 3/4 infections affecting 15%, underscoring the need for proactive monitoring and preventative measures.
Impressive Early Efficacy Data
The preliminary efficacy results are compelling. After 8 cycles of cevostamab, 81% of evaluable patients achieved a stringent complete response (sCR), and an astonishing 95% were MRD-negative at a sensitivity of 10-5. Even more encouraging, at 12 months post-CAR T-cell therapy, 93% of patients maintained this MRD-negative sCR. These deep remissions translated into exceptional progression-free and overall survival rates, both estimated at 95% at 12 months. These data suggest that consolidating with cevostamab can significantly improve long-term outcomes for patients with RRMM.
The Future of Myeloma Treatment: Sequential Therapies
These findings support a growing trend in myeloma treatment: sequential therapies designed to overcome resistance mechanisms and deepen responses. The “STEM” trial exemplifies this approach, leveraging the power of CAR T-cell therapy followed by targeted consolidation with cevostamab. Further research will focus on identifying biomarkers to predict which patients are most likely to benefit from this strategy and optimizing the duration and timing of cevostamab administration. The potential for combining cevostamab with other novel agents, such as bispecific antibodies targeting different antigens, is also an exciting area of investigation. Learn more about bispecific antibodies from the National Cancer Institute.
What are your predictions for the role of sequential therapies in myeloma treatment? Share your thoughts in the comments below!
