Real-world pharmacovigilance of BCMA-targeted CAR-T therapy in refractory multiplemyeloma: A comparative analysis of idecabtagene vicleucel and ciltacabtagene autoleucel

Abstract

Abstract Background: B-cell maturation antigen (BCMA)-directed CAR-T therapies have redefined care for relapsed and refractory multiple myeloma, delivering durable remissions in heavily pre-treated patients. The two FDA-approved products—idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) show impressive efficacy, yet head-to-head safety evidence in real-world practice remains sparse, highlighting the need for robust post-marketing pharmacovigilance. Methods FDA adverse event reporting system (FAERS) data through May 2024 were queried for Ide-cel and Cilta-cel. Nine prespecified adverse events were assessed, namely cytokine-release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), other neurotoxic events, pyrexia, fatigue, anemia, neutropenia, hypotension, and plasma-cell myeloma. For each event, 2 × 2 contingency tables (drug × event) were constructed. Disproportionality was quantified as (i) risk ratio (RR) and (ii) reporting-odds ratio (ROR), both with 95% Wald/Woolf confidence intervals. Two-sided p-values were obtained using Fisher's exact test. All analyses were conducted with Stata 18. Results A total of 4201 post-marketing adverse event (AE) reports related to BCMA-directed CAR-T therapies were retrieved from the FAERS database, comprising 961 reports for Ide-cel and 3240 for Cilta-cel. Among reports with available demographics, patients receiving Ide-cel were predominantly male (48.9%) and aged between 65–85 years (42.5%). For Cilta-cel, the majority of reports were from recent years (2024–2025). Disproportionality analysis revealed consistently higher reporting of several adverse events with Ide-cel. CRS was reported more than twice as frequently with Ide-cel compared to Cilta-cel (RR 2.36; ROR 4.25, 95% CI 3.67–4.92). ICANS was also significantly more frequent with Ide-cel (RR 2.04; ROR 2.25, 95% CI 1.84–2.75), as were fatigue (RR 2.61; ROR 2.93), anemia (RR 3.11; ROR 3.36), and neutropenia (RR 2.42; ROR 2.50). Broad neurotoxicity, which includes but is not limited to ICANS, showed a modestly elevated risk with Ide-cel (RR 1.56; ROR 1.60, 95% CI 1.19–2.15). Conclusion In this large real-world pharmacovigilance analysis, idecabtagene vicleucel was associated with significantly higher reporting of CRS, ICANS, anemia, neutropenia, fatigue, and broad neurotoxicity compared with ciltacabtagene autoleucel, whereas no excess signal emerged for hypotension or secondary plasma-cell myeloma. These data suggest a distinct safety profile for each BCMA-directed CAR-T product that should inform patient selection, pre-emptive monitoring, and supportive-care strategies in routine practice. Continued post-approval surveillance and prospective comparative studies are warranted to refine risk-mitigation approaches and optimize outcomes for patients with relapsed and refractory multiple myeloma.