Fatal infection–associated adverse events with B-cell maturation antigen–directed therapies in multiple myeloma: A FAERS pharmacovigilance study.

Abstract

e19552 Background: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies have transformed the treatment landscape for relapsed or refractory multiple myeloma. However, infectious complications remain a major source of morbidity and mortality, particularly in heavily pretreated patients. Real-world patterns of fatal infection-associated adverse events across BCMA-directed platforms have not been systematically characterized in post-marketing surveillance. Methods: We performed a retrospective pharmacovigilance analysis of the U.S. FDA Adverse Event Reporting System (FAERS) to evaluate FDA-approved BCMA-directed therapies (idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), teclistamab, elranatamab, and talquetamab) from approval through the end of 2024. Primary or secondary suspected drug reports (PS+SS) were included, with sensitivity analyses restricted to primary suspect reports. Fatal infection–associated events were defined as death with concurrent infection-related MedDRA preferred terms; secondary endpoints included fatal cytopenia, fatal cytokine release syndrome (CRS), and a serious adverse event composite. Duplicate reports were excluded using standard FAERS de-duplication methods, with primary approval-aligned analyses and calendar-window sensitivity analyses. Results: Across approval-aligned windows, 7,280 BCMA-directed adverse event reports were identified. Fatal infection–associated events were most frequently reported with teclistamab (187/2,397 reports; 612 deaths), followed by cilta-cel (71/2,366; 301 deaths), elranatamab (45/792; 157 deaths), ide-cel (23/972; 125 deaths), and talquetamab (21/753; 73 deaths). Fatal CRS-associated events were observed across agents, most commonly with cilta-cel (83) and teclistamab (74). Calendar-window sensitivity analyses (2022–2024) demonstrated consistent relative ranking, and primary-suspect-only analyses showed similar directional patterns. Conclusions: In this real-world FAERS analysis, BCMA-directed therapies exhibited distinct post-marketing safety profiles, with a substantial burden of infection-associated fatal events, particularly among bispecific antibodies. CRS- and cytopenia-associated fatalities were observed across agents, and serious non-fatal adverse events were common. These findings highlight heterogeneity in safety signals across BCMA platforms and underscore the need for continued post-marketing surveillance and agent-specific infection risk mitigation strategies in heavily pretreated multiple myeloma populations.