What question did this study set out to answer?

This analysis aims to consolidate and compare the adverse event profiles of approved CAR-T therapies using pharmacovigilance methods.

July 1, 2026Open Access

Adverse Events of CD19- and BCMA-Directed Chimeric Antigen Receptor T-Cell Therapy: An Analysis of the FDA Adverse Events Database

Key Points

This analysis aims to consolidate and compare the adverse event profiles of approved CAR-T therapies using pharmacovigilance methods.
Disproportionality analyses were performed using the FDA Adverse Events Reporting System (FAERS) and OpenVigil 2.1.
Analysis stratified by target antigen for both anti-CD19 and anti-BCMA agents.
Calculations of event counts, reporting odds ratios, proportional reporting ratios, and chi-squared statistics for the 25 most frequently reported AEs.
36,567 adverse events were identified across all six CAR-T therapies.
Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were the most frequent adverse events with RORs exceeding 240 for all agents.
Ciltacabtagene autoleucel exhibited unique neurological adverse events, while brexucabtagene autoleucel indicated secondary malignancy signals.

Abstract

Background: Chimeric antigen receptor T-cell (CAR-T) therapies have transformed the treatment of haematologic malignancies, yet their adverse event (AE) profiles across all approved agents have not been consolidated using a pharmacovigilance methodology in a single comparative analysis. Methods: Using the FDA Adverse Events Reporting System (FAERS) and OpenVigil 2.1, disproportionality analyses for all six FDA-approved CAR-T therapies were performed, stratified by target antigen: anti-CD19 agents (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel) and anti-BCMA agents (idecabtagene vicleucel, ciltacabtagene autoleucel). For each of the 25 most frequently reported AEs per agent, the report event counts, reporting odds ratio (ROR) with 95% confidence interval, proportional reporting ratio (PRR), and chi-squared statistic were calculated. Results: A total of 36,567 AEs were identified across all six agents. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were the most frequent and most disproportionate AEs across all six therapies, with RORs exceeding 240 in every agent. Idecabtagene vicleucel had the highest ROR for cytokine release syndrome among all agents (ROR 1934.6), while brexucabtagene autoleucel had the highest ROR for immune effector cell-associated neurotoxicity syndrome (ROR 2089.6). Ciltacabtagene autoleucel exhibited a unique neurological toxicity profile, cranial nerve paralysis (ROR 3167.6, PRR 3055.0, chi2 199,190), parkinsonism (ROR 145.5, PRR 136.6, chi2 24,840), Bell’s palsy (ROR 380.4, PRR 370.3), and facial paralysis (ROR 72.7), consistent with the late neurotoxicity syndrome previously characterized, and absent from other agents’ top 25 AE lists. Brexucabtagene autoleucel demonstrated secondary malignancy signals including squamous cell carcinoma of skin (ROR 308.2) and myelodysplastic syndrome (ROR 97.9). Tisagenlecleucel showed the highest hypogammaglobulinemia signal among all agents (ROR 614.1, PRR 536.5, chi2 144,832) alongside a broad pancytopenia profile. Hemophagocytic lymphohistiocytosis was a significant finding with ciltacabtagene autoleucel (ROR 71.0) and brexucabtagene autoleucel (ROR 57.8). Conclusions: CAR-T therapies share class-wide toxicities in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, but exhibit clinically important drug-specific and target-class-specific AE profiles. This consolidated FAERS-based analysis corroborates and extends prior pharmacovigilance work by providing direct cross-agent comparisons, and supports the use of agent-tailored monitoring strategies, particularly for the distinctive late neurological toxicity associated with ciltacabtagene autoleucel.

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