Immune effector cell-associated hematotoxicity following CAR-T cell therapies: insights from a large national...

Immune effector cell-associated hematotoxicity is a recognized but incompletely characterized complication of chimeric antigen receptor T-cell (CAR-T) therapy, defined by prolonged, severe, or recurrent cytopenias following CAR-T infusion, not explained by conditioning chemotherapy or disease progression alone. Despite formal consensus grading criteria from the European Hematology Association and European Bone Marrow Transplantation group, the post-marketing pharmacovigilance profile of ICAHT across all approved CAR-T agents has not been systematically described. The FDA Adverse Event Reporting System (FAERS) was queried through March 2026 using OpenVigil 2.1 for all seven currently FDA-approved CAR-T products. Disproportionality was assessed using the Reporting Odds Ratio (ROR) with 95% confidence intervals, Proportional Reporting Ratio with chi-squared statistic, and Bayesian Reporting Rate Ratio. An adverse drug reaction classification was applied when all three signal detection thresholds were simultaneously met. ICAHT cases were identified in five of seven agents. Axicabtagene ciloleucel had the highest case count (n = 18) and most precisely estimated ROR (1365.54; 95% CI: 778.83-2394.24). All five agents with ICAHT reports met pre-specified signal detection criteria across all three analytical methods, with lower ROR confidence bounds substantially exceeding 1.00 in every case. No ICAHT reports were identified for obecabtagene autoleucel or tisagenlecleucel, with the former having minimal post-marketing data and the latter potentially reflecting genuine mechanistic differences related to its 4-1BB co-stimulatory domain. These findings demonstrate that ICAHT generates exceptionally strong and concordant pharmacovigilance signals across multiple CAR-T products, supporting heightened post-infusion hematologic monitoring with a low threshold for investigating unexplained cytopenias.