Eosinophil‐induced adverse events induced by treatment with programmed cell death 1/ligand 1 inhibitors: A comprehensive disproportionality analysis of the FDA adverse event reporting system

Eosinophil-induced adverse events (Eo-irAEs) have been observed in patients treated with programmed cell death 1/ligand 1 (PD-1/PD-L1) inhibitors. Surprisingly, the clinical features and outcomes of Eo-irAEs induced by PD-1/PD-L1 inhibitors have not yet been elucidated. This study investigated the characteristics of and risk factors for Eo-irAEs induced by PD-1/PD-L1 inhibitors. We extracted data on Eo-irAEs related to PD-1/PD-L1 inhibitors from the FDA Adverse Event Reporting System (FAERS) from 2015 to 2023. Disproportionality and Bayesian analyses were applied for data mining and analysis. A total of 430 Eo-irAEs induced by PD-1/PD-L1 inhibitors were included in this study. Older male patients were found to be at a high risk of developing Eo-irAEs. Cemiplimab (ROR 2.66 [1.38, 5.13]), nivolumab (ROR 1.82 [1.61, 2.05]), and pembrolizumab (ROR 1.35 [1.13, 1.62]) showed stronger signals than the other drugs. Cemiplimab showed higher signals for Eo-irAEs than other PD-1/PD-L1 inhibitors, with an information component (IC) of 1.41 (IC 0.25:0.73). Patients experienced Eo-irAEs within the first 100 days, with a median onset time of 56 (interquartile range: 17.0-169.0) days. Eo-irAEs were more likely to occur in patients with lung (n = 147, 34.83%) and skin tumors (n = 145, 34.36%). Eosinophilia (n = 193, 44.88%), drug reactions with eosinophilia and systemic symptoms (DRESS) (n = 98, 22.79%), and eosinophilic fasciitis (n = 69, 16.05%) were the most common adverse events. Eo-irAEs that were life-threatening or resulted in death comprised 5.15% (n = 21) and 5.39% (n = 22) of the patients. PD-1/PD-L1 inhibitors used across a broad spectrum of cancers are associated with an increased risk of Eo-irAEs, which tend to occur early. Although these complications are rare, clinicians using PD-1/PD-L1 inhibitors should be aware of and monitor these potentially serious adverse events related to Eo-irAEs.