DOP114Colitis Reporting in the Era of CAR-T Cell Therapies: Opposing Signals from Global Pharmacovigilance Data

Abstract Background As the use of chimeric antigen receptor (CAR) T-cell therapies expands, isolated cases of immune-mediated colitis (IMC) following B-cell maturation antigen (BCMA)-directed products have been reported. In contrast, despite broader clinical experience, IMC following CD19-directed CAR-T therapies has been only rarely described, and emerging early clinical data suggest potential therapeutic benefit in refractory ulcerative colitis. We therefore aimed to investigate the bidirectional relationship between different CAR-T constructs and IMC using real-world pharmacovigilance data. Methods A retrospective, pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) from January 2017 to June 2025. The primary outcome was IMC reporting. Reporting odds ratios (RORs) were calculated to compare IMC reporting among CAR-T recipients with other oncological patients, adjusted for age and sex. Results The FAERS database included 14,828 eligible CAR-T-related safety reports, of which 3,883 were associated with BCMA-directed products (idecabtagene vicleucel, ciltacabtagene autoleucel, and obecabtagene autoleucel) and 10,945 with CD19-directed products. The median patient age was 64 (IQR 54-70), and 39% were female. IMC reporting was significantly higher following BCMA-directed CAR-T compared with other oncological patients (37 cases; ROR=15.25 95% CI: 10.90 − 21.32, p 0.001). In contrast, IMC was less frequently reported after CD19-directed CAR-T therapy, although not significantly (n = 4, ROR=0.51 0.19 − 1.38, p = 0.186). In a sensitivity analysis applying an expanded set of colitis terms, IMC reporting remained significantly elevated with BCMA-directed CAR-T therapy (ROR=4.18 3.40 − 5.14, p 0.001), and was significantly reduced among CD19-directed CAR-T recipients (ROR=0.48 0.33 − 0.68, p 0.001). Among CAR-T–related IMC cases, 13 (32%) required hospitalization, and 7 (17%) were fatal. Importantly, only 5 (12%) cases reported concomitant cytokine release syndrome. Conclusion This global pharmacovigilance study identified a novel safety concern of IMC following BCMA-directed CAR-T therapy, but not after CD19-directed constructs. These findings suggest a distinct, target-dependent effect of CAR-T therapy on intestinal immunity. References: 1.Swan D., Madduri D., Hocking J. CAR-T cell therapy in Multiple Myeloma: current status and future challenges. Blood Cancer J 2024. Doi: 10.1038/s41408-024-01191-8. 2.Fortuna GG., Banerjee R., Savid-Frontera C., Song J., Morán-Segura CM., Nguyen J V., et al. Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma. Blood Cancer J 2024;14(1). Doi: 10.1038/s41408-024-01167-8. 3.Lim KJC., Chhabra S., Corraes ADMS., Parrondo RD., Gertz M., Hwa L., et al. Risk Factors for Immune Effector Cell-Associated Enterocolitis (IEC-colitis) in Patients with Relapsed Myeloma Treated with Ciltacabtagene Autoleucel (cilta-cel). Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy 2025;31(2):S234–5. Doi: 10.1016/j.jtct.2025.01.357. 4.Müller F., Atreya R., Völkl S., Aigner M., Kretschmann S., Kharboutli S., et al. CD19 CAR T-Cell Therapy in Multidrug-Resistant Ulcerative Colitis. New England Journal of Medicine 2025;393(12):1239–41. Doi: 10.1056/nejmc2508023. Conflict of interest: Cohen, Yaron: None Shouval, Roni: No conflict of interest Mayer, Chen: No conflict of interest Ukashi, Offir: NA Levartovsky, Asaf: Honoraria and speaker fees from: Takeda, Sanofi, Rafa Ben-Horin, Shomron: Grant: Abbvie, Takeda, Janssen, Celltrion, Pfizer, Medtronic, Galmed, OutSense Personal Fees: Advisory board and/or consulting and/or Speaker fees from Abbvie, Takeda, Janssen, Celltrion, Pfizer, GSK, Ferring, Novartis, Roche, Gilead, NeoPharm, EviNature, Galmed, Medial Earlysign, BMS, Pfizer, Falk, Medtronic and Eli Lilly. Options/stocks in Predicta Med, Evinature, Galmed, Alma Therpeautics. Goldman, Adam: No conflict of interest