Association of ciltacabtagene autoleucel with immune effector cell-associated enterocolitis: insights from a large national database

Effector Cell-Associated Enterocolitis Following Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma" by Fortuna and colleagues with great interest 1.The article provides valuable insight into rare but serious toxicities of CAR T-cell therapies that are not fully characterized in phase 3 trial data.Given the designation of immune effector cell-associated enterocolitis (IEC-EC), this was the first, and largest, case series describing acute severe nonbloody diarrhea and gut inflammation weeks to months after CAR T-cell therapy without infectious cause.Subsequent reports prompted a warning issued from the FDA regarding the risk of IEC-EC in patients treated with ciltacabtagene autoleucel.We were interested in the national reporting of this event within the FDA Adverse Event Reporting System (FAERS) across multiple institutions for all commercial CAR T-cell therapies, aiming to understand if this adverse event is associated with the disease, target antigen, or specific CART construct.Immune-mediated adverse events, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common side effects of CAR T-cell therapy.Both the product and underlying disease contribute to rates of CRS and ICANS, though they can be seen in up to 93% and 87% of patients, respectively.Additionally, unique and unexpected toxicities have been identified in longer term follow-up of patients treated with CAR T-cell therapy 2.The emergence of these toxicities harkens to the need for ongoing pharmacovigilance, such is the case for IEC-EC.To address this unmet need, epidemiological data were extracted from the FAERS database, as previously described 3.To address this unmet need, epidemiological data were extracted from the FAERS database, as previously described 3.Data from January 1, 2013, through October 13, 2025, were queried using OpenVigil 2.1, which implements automated data cleaning (deduplication, formatting correction, and drug name harmonization).Analyses included only records designating the drug as the primary suspect.Missing demographic and severity data, as well as time-to-onset, were unavailable through OpenVigil and thus excluded.Both serious and non-serious events were analyzed.Cases were identified using the MedDRA Preferred Term (PT) "immune-mediated enterocolitis".Data were retrieved for all six FDA-approved CAR T-cell therapies.Signal detection employed disproportionality analysis using the reporting odds ratio (ROR) derived from 2 2 contingency tables.A signal was considered significant if ROR > 2.0 and the lower 95% confidence interval