Neurotoxicity and rare adverse events in BCMA-Directed CAR t cell therapy: A comprehensive analysis of real-world FAERS data Journal Article
| Authors: | Ellithi, M.; Elsallab, M.; Lunning, M. A.; Holstein, S. A.; Sharma, S.; Trinh, J. Q.; Ma, J.; Maus, M. V.; Frigault, M. J.; D'Angelo, C. R. |
| Article Title: | Neurotoxicity and rare adverse events in BCMA-Directed CAR t cell therapy: A comprehensive analysis of real-world FAERS data |
| Abstract: | 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, the identification and management of associated rare toxicities become increasingly crucial. This study aims 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). We performed 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, Parkinson's disease and parkinsonism, and 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 to 47.5), intracranial hemorrhage and cerebrovascular accidents (ROR: 2.9, 95% CI 1.8 to 4.8), Haemophilus infections (ROR: 34.2, 95% CI 11.8 to 98.9) and cytomegalovirus infections (ROR: 3.9, 95% CI 1.6 to 9.5). For ide-cel, new signals included parkinsonism (ROR: 13.7, 95% CI 5.5 to 34.5), acute and chronic sarcoidosis (ROR: 197.1, 95% CI 32.9 to 1180.1), ventricular arrhythmias, and cardiac arrest (ROR: 3.9, 95% CI 2.1 to 7.3). This analysis provides a comprehensive insight into the safety profiles of the commercial BCMA-directed CAR T therapies, underscoring the importance of vigilant post-marketing surveillance to mitigate potential risks. © 2024 The American Society for Transplantation and Cellular Therapy |
| Keywords: | adult; treatment response; aged; major clinical study; fatigue; drug safety; side effect; united states; united states food and drug administration; neurotoxicity; liver toxicity; breast cancer; anemia; myalgia; lung cancer; kidney failure; food and drug administration; prostate cancer; hypoxia; chronic disease; acute kidney failure; confusion; hypoalbuminemia; hypotension; malaise; t cell lymphoma; immunology; acute leukemia; myelodysplastic syndrome; adverse drug reaction reporting systems; brain disease; sepsis; chimeric antigen receptor; colitis; cross-sectional study; cross-sectional studies; safety; pancytopenia; hyperbilirubinemia; bacteremia; seizure; virus infection; headache; product labeling; meningioma; second cancer; heart arrhythmia; somnolence; immune deficiency; epidemiology; motor dysfunction; aphasia; parkinson disease; coma; epilepsy; immunoglobulin deficiency; postmarketing surveillance; neurologic disease; tremor; sarcoidosis; t cell leukemia; brain hematoma; cranial nerve paralysis; cytopenia; brain hemorrhage; hemiparesis; adverse drug reaction; facial nerve paralysis; cytomegalovirus infection; adoptive immunotherapy; immunotherapy, adoptive; immunopathology; tachycardia; viral upper respiratory tract infection; virus pneumonia; hematologic disease; heart arrest; enterococcal infection; myeloma; cerebrovascular accident; acute disease; rare disease; respiratory failure; hemophagocytic syndrome; enterocolitis; gastroenteritis; hemiplegia; thrombotic microangiopathy; etiology; myeloid leukemia; bone marrow depression; adverse event; decreased appetite; acute respiratory failure; disorientation; viremia; septic shock; hyperammonemia; capillary leak syndrome; nerve paralysis; oliguria; stridor; anaplastic large cell lymphoma; guillain barre syndrome; appetite disorder; cytokine release syndrome; parkinsonism; acute myeloid leukemia; consciousness disorder; haemophilus infection; fda; polyneuropathy; brain toxicity; oculomotor nerve disease; neurotoxicity syndromes; larynx edema; ischemic stroke; non melanoma skin cancer; escherichia coli infection; disseminated intravascular clotting; fungemia; rhinovirus infection; infusion related reaction; respiratory arrest; humans; human; male; female; article; hypergammaglobulinemia; pseudomonas infection; drug packaging; b cell maturation antigen; balance disorder; metabolic encephalopathy; pharmacovigilance; b-cell maturation antigen; chimeric antigen receptor t-cell immunotherapy; bell palsy; car t; immune effector cell associated neurotoxicity syndrome; receptors, chimeric antigen; ciltacabtagene autoleucel; idecabtagene vicleucel; torsade de pointes; intestinal t cell lymphoma; altered state of consciousness; postmarketing; cilta cel; ide cel; cogwheel rigidity; dysdiadochokinesis; dysgraphia; enterococcal bacteremia; focal seizures; hypophagia; metapneumovirus infection; neutropenic colitis |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 31 |
| Issue: | 2 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-02-01 |
| Start Page: | 71.e1 |
| End Page: | 71.e14 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2024.12.002 |
| PUBMED: | 39672542 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
