Neurotoxicity and Rare Adverse Events in BCMA-Directed CAR T Cell Therapy: A Comprehensive Analysis of Real-World FAERS Data

•Neurotoxic adverse events were observed in both cilta-cel and ide-cel, with distinct manifestations. Cilta-cel neurotoxicity manifested as cranial nerve palsies, parkinsonism, and polyneuropathies, while ide-cel was associated with confusion, disorientation, seizures, and tremors.•Significant safety signals were detected for cerebrovascular accidents, intracranial hemorrhage, and haemophilus and cytomegalovirus infections in cilta-cel.•New safety signals were detected for parkinsonism, sarcoidosis, ventricular arrhythmias, and cardiac arrest in ide-cel.•The study underscores the importance of ongoing surveillance of long-term adverse outcomes in patients receiving CAR-T therapies. Chimeric antigen receptor T (CAR T) cell therapies have emerged as a valuable treatment modality for patients with plasma cell disorders. As the population of patients receiving CAR T therapies grows, identification and management of associated rare toxicities have become increasingly crucial. To identify safety signals associated with commercial anti-B-cell maturation antigen (BCMA) CAR T therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS). This is a cross-sectional analysis of the adverse events (AE) reports associated with ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), submitted to FAERS between January 2021 and December 2023. AE frequencies were summarized using descriptive statistics, and safety signals were explored by measuring the reporting odds ratio (ROR) compared to control groups. Among 4,472,782 unique FAERS reports, 1,496 involved BCMA-directed CAR-T therapies. AEs reported more frequently included immune associated conditions and neurological disorders. Neurotoxicity associated with cilta-cel predominantly manifested as cranial nerve palsies, parkinsonism, acute and chronic polyneuropathies, while ide-cel neurotoxicity presented as confusion, disorientation, seizures, balance disturbances, and tremors. In cilta-cel reports, other safety signals included Guillain-Barre syndrome (ROR: 17.1, 95% CI 6.1 -47.5), intracranial hemorrhage and cerebrovascular accidents (ROR: 2.9, 95% CI 1.8 -4.8), haemophilus infections (ROR: 34.2, 95% CI 11.8-98.9) and cytomegalovirus infections (ROR: 3.9, 95% CI 1.6 -9.5). For ide-cel, new signals included parkinsonism (ROR: 13.7, 95% CI 5.5-34.5), acute and chronic sarcoidosis (ROR: 197.1, 95% CI 32.9 -1180.1), ventricular arrhythmias, and cardiac arrest (ROR: 3.9, 95% CI