Abstract / Summary
Programmed cell death 1/ligand 1 (PD-1/PD-L1) inhibitors have revolutionized cancer treatment. With their widespread clinical application, immune-associated adverse events (irAEs) have become a major concern. Immune thrombocytopenia (ITP) is an uncommon hematological immune-associated adverse event reported during PD-1/PD-L1 inhibitors treatment. Its comprehensive clinical and epidemiological characteristics remain incompletely characterized. PD-1/PD-L1-associated ITP events were retrieved from the United States Food and Drug Administration (FDA) Adverse Event Monitoring System (AEMS) and the Japanese Adverse Drug Event Report (JADER) database between January 2015 and June 2025. Disproportionality analyses including reporting odds ratio (ROR) and Bayesian methods were used for signal detection, and exploratory multivariable logistic regression was performed to identify report-level factors. In AEMS, 288 ITP reports were identified among 157,788 reports involving PD-1/PD-L1 inhibitors (0.18%), with men accounted for 53.8% and individuals aged ≥ 65 years accounted for 58.4%. The median time to onset (TTO) was 43.0 (interquartile range, 13.0–126.0) days. All PD-1/PD-L1 inhibitors demonstrated significant disproportionality signals. The Weibull shape parameter was β = 0.70 (95% CI 0.64–0.80), consistent with an early-failure pattern. After excluding reports from Japan, positive disproportionality persisted [ROR, 5.72; 95% CI, 4.83–6.77]. Multivariable logistic regression showed that patients age 65–85 years and ≤ 75 kg had a higher risk of ITP reporting. In JADER, 322 ITP reports were identified among 69,205 relevant reports (0.47%), with an overall ROR of 3.57 (95% CI, 3.13–4.06). PD-1/PD-L1 inhibitors showed disproportionate reporting of ITP in AEMS and JADER. Reports clustered early after treatment initiation but were also recorded later, and exploratory analysis identified age- and weight-associated reporting patterns. These findings support early attention to platelet changes and continued clinical vigilance during ICI treatment, while providing priorities for active-surveillance studies.