Abstract
Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancers. With their increased use and prolonged treatment duration, immune-related adverse events (irAEs)—including hematologic toxicities—are increasingly recognized. So a better understanding of specific hematologic adverse events (hAEs) is essential. We aimed to evaluate disproportionality signals for hAEs linked to ICIs using real-world data from the FDA Adverse Event Reporting System (FAERS).Methods: We performed a retrospective analysis of FAERS reports submitted between Q1 2013 and Q1 2025. We employed 8 ICIs (including the brand and generic names)—atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and tremelimumab in the analysis. Hematologic AEs were defined using a curated MedDRA dictionary, encompassing cytopenias (anemia, neutropenia, thrombocytopenia, pancytopenia, bicytopenia), immune-mediated cytopenias (e.g., immune thrombocytopenia, autoimmune hemolytic anemia), bone marrow failure, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myelosuppression, lymphoma, and coagulation disorders. Disproportionality analysis was conducted using Reporting Odds Ratio (ROR) with 95% confidence intervals (CI) and Bayesian Information Component (IC) with 95% credibility intervals. Signals were considered positive when the lower bound of the ROR exceeded 1 and the IC exceeded 0.Results: Total AEs reported were 569880, and of these, 3.1% were hAEs. Immune thrombocytopenia emerged as the most consistent and robust signal across all ICIs evaluated. The strongest associations were observed for tremelimumab (ROR 72.98, 95% CI 20.98–253.84; IC 6.17, 95% CI 4.40–7.95), cemiplimab (ROR 19.65, 95% CI 8.50–45.43; IC 4.29, 95% CI 3.09–5.49), and durvalumab (ROR 17.19, 95% CI 12.50–23.66; IC 4.08, 95% CI 3.63–4.53). Other notable findings included febrile neutropenia with atezolizumab (ROR 2.17; IC 1.11) and myelosuppression with durvalumab (ROR 4.31; IC 2.10). Cemiplimab also demonstrated elevated signals for bicytopenia (ROR 7.83; IC 2.97) and pancytopenia (ROR 1.99; IC 0.99). Broader cytopenia categories, such as anemia and neutropenia, did not consistently show significant associations, highlighting the importance of distinguishing specific hAEs. Notably, all eight ICIs demonstrated at least one statistically significant hematologic safety signal.Conclusions: This large, real-world pharmacovigilance study provides comprehensive insight into hematologic adverse events associated with ICIs. Immune thrombocytopenia was the most prominent signal across agents, with additional drug-specific patterns observed. These findings underscore the need for focused monitoring strategies and may inform clinical decision-making and future prospective safety evaluations.
