Cevostamab, a FcRH5xCD3 bispecific antibody, shows promising results in heavily treated patients with relapsed/refractory multiple myeloma (RRMM). In a Phase I study, it demonstrated dose-dependent efficacy and manageable safety profiles, particularly at the 160mg target dose level administered every 3 weeks. The treatment achieved an overall response rate of 43.1%, with notable responses including stringent complete responses and very good partial responses. Common adverse events included cytokine release syndrome and neutropenia, which were generally manageable. These findings suggest cevostamab's potential as a therapeutic option in advanced MM.

Key Points:

• Cevostamab is a FcRH5xCD3 bispecific antibody targeting MM cells.
• Phase I study (NCT03275103) evaluated its efficacy in RRMM patients.
• Overall response rate (ORR) was 43.1%, with a significant proportion achieving stringent complete responses (6.6%).
• Median duration of response was 10.4 months.
• Most patients (95.8%) were triple-class refractory, highlighting the study's focus on heavily pretreated individuals.
• Common adverse events (>20%) included cytokine release syndrome (74.3%) and neutropenia (31.1%).
• CRS management strategies included tocilizumab and steroids.
• Treatment-related adverse events led to discontinuation in 6.6% of patients.
• Study included patients with high-risk cytogenetics and extramedullary disease.
• Future studies may explore combination therapies and alternative dosing regimens.

Authors:
Joshua Richter, MD; Sheeba K. Thomas, MD; Amrita Y. Krishnan, MD, FACP; Jacob P. Laubach; Adam D. Cohen, MD; Suzanne Trudel, MD, MSc; Luciano J. Costa, MD, PhD; Nizar J. Bahlis, MD; Peter A. Forsberg, MD; Rayan Kaedbey