Abstract
BACKGROUND: This study aimed to characterize the risk signals and clinical features of pembrolizumab-associated neutropenia reported as serious adverse events (SAEs) in the US FDA Adverse Event Reporting System (FAERS), and the association between concomitant chemotherapy and time-to-onset. METHODS: In this retrospective pharmacovigilance study, SAE reports from FAERS (2021Q1–2024Q2) with pembrolizumab designated as the primary suspect drug were analyzed. Among 14,747 pembrolizumab-associated SAE reports, 856 with the Preferred Term “neutropenia” were identified and characterized. Clinical characteristics were summarized, and subgroup analyses explored associations between concomitant chemotherapy and TTO, as well as between sex and the reporting odds ratio (ROR). A supplementary analysis of febrile neutropenia (FN) cases was conducted to assess clinical severity. RESULTS: Among 14,747 SAEs, 856 were neutropenia cases, for which a strong signal of disproportional reporting was detected (ROR = 5.23, 95% CI: 4.88–5.60). Median patient age was 61.0 years, and the reported mortality rate was 19.4%. A higher ROR was observed in females (7.06) than males (4.42), a difference likely influenced by the underlying distribution of cancer types and the 9.8% missing data for sex, rather than indicating an intrinsic sex-related risk. The overall median TTO was 19.0 days, with the concomitant chemotherapy group (N = 268) showing a shorter median TTO (14.5 days) than the non-chemotherapy group (N = 55, 39.0 days; p = 0.0006). Among 311 FN cases, 86.5% (269/311) occurred in the concomitant chemotherapy group. CONCLUSION: Pembrolizumab-associated neutropenia represents a notable safety signal in FAERS. The observed early-onset pattern, particularly in the context of concomitant chemotherapy, provides real-world evidence characterizing the clinical features of this adverse event.