A Real-World Pharmacovigilance Study of Adverse Drug Reactions to CD19- and BCMA-Targeted CAR-T Cell Therapies

To evaluate the clinical safety of four CD19-targeted and two BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapies.

Adverse drug reaction (ADR) reports for six CAR-T products (Breyanzi, Kymriah, Tecartus, Yescarta, Abecma, Carvykti) from the US FDA Adverse Event Reporting System (FAERS) database between January 2004 and March 2025 were retrieved. The basic characteristics of the reports were analyzed. ADRs were categorized by System Organ Class (SOC) and coded into corresponding preferred term(PT) using MedDRA (Version 27.1). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to detect association signals between the six drugs and the PT.

A total of 54 833 ADR reports were included in this study: Breyanzi (1511, 2.76%), Kymriah (18 087, 32.99%), Tecartus (4408, 8.04%), Yescarta (23 937, 43.65%), Abecma (2762, 5.04%), and Carvykti (4128, 7.53%). These reports corresponded to 15 210 unique patients, comprising 7136 males (46.92%), 4483 females (29.47%), and 3591 (23.61%) with missing gender information. Regarding age distribution, all patients in the Abecma and Carvykti groups were ≥18 years old, while 22.52% of patients in the Kymriah group were < 18 years old. The proportion of male patients was higher than that of females across all six drug groups. The top seven ADRs by report count were, in order: various nervous system disorders; immune system disorders; general disorders and administration site conditions; various investigations; infections and infestations; various neoplasms; and blood and lymphatic system disorders. The top ten PTs by report count included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), pyrexia, neurotoxicity, death, hypotension, disease progression, fatigue, platelet count decreased, and malignant neoplasm progression. Among the six CAR-T therapies, the BCMA-targeted Abecma showed the strongest association with CRS [ROR 2412.12(95% CI: 2093.06-2779.83), PRR 891.75(χ²=449 083.34)]. The CD19-targeted Tecartus showed the strongest association with ICANS [ROR 2604.50 (95% CI: 2317.29-2927.30), PRR 1775.36 (χ²=705 195.47)] and neurotoxicity [ROR 762.84(95% CI: 685.77-848.56), PRR 439.88 (χ²=254 246.08)].All drugs except Tecartus were associated with decreased platelet count. Furthermore, both Breyanzi and Kymriah were associated with malignant neoplasm progression.

Clinicians should implement rigorous safety monitoring for patients receiving CAR-T therapy, paying particular attention to the early symptoms of CRS and neurotoxicity, and enhance surveillance for malignant neoplasm progression.