Autoimmune cytopenias associated with immune checkpoint inhibitors: A disproportionality analysis of FAERS.

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Background: Immune checkpoint inhibitors (ICIs) enhance antitumor immunity but may disrupt peripheral tolerance, leading to immune-related adverse events. While dermatologic, endocrine, and gastrointestinal toxicities are well described, immune-mediated hematologic complications remain incompletely characterized. We evaluated the association between ICIs and autoimmune cytopenias using a large-scale pharmacovigilance database. Methods: We conducted a retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) from 2011 through 2025. ICIs were grouped as CTLA-4, PD-1, and PD-L1 inhibitors. Autoimmune cytopenias were defined using MedDRA preferred terms including autoimmune hemolytic anemia, immune thrombocytopenia, autoimmune neutropenia, and immune-mediated pancytopenia. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated comparing ICIs with all other drugs in FAERS. Internal class comparisons were performed. Serious outcomes, including death, were evaluated. Results: Among 268,135 ICI reports, 794 autoimmune cytopenia cases were identified (0.30%), compared with 11,254 cases among 32,473,224 non-ICI reports. ICIs demonstrated significant disproportionate reporting of autoimmune cytopenias (ROR 8.6, 95% CI 8.0–9.2). Signals were observed across all classes: CTLA-4 (99/34,519; 0.29%), PD-1 (607/177,425; 0.34%), and PD-L1 inhibitors (170/56,191; 0.30%), without marked differences between subclasses. Death was reported in 15.2% of CTLA-4, 16.1% of PD-1, and 17.6% of PD-L1 cytopenia cases. Conclusions: Immune checkpoint inhibitors are associated with strong disproportionate reporting of autoimmune cytopenias in FAERS, with consistent signals across drug classes and notable fatality proportions. Although causality cannot be established from spontaneous reporting data, these findings highlight rare but potentially life-threatening hematologic immune toxicities that warrant heightened clinical awareness and early diagnostic evaluation.