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

We have read the intriguing article entitled “Immune 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 non-bloody 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.