Unveiling the hidden cardiovascular risk of sipuleucel-T: a pharmacovigilance analysis using the FDA Adverse Event Reporting System, 2010–2025

Background Sipuleucel-T, the first therapeutic cancer vaccine approved by the U.S. Food and Drug Administration (FDA), represents a crucial treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, the characteristics of cardiovascular adverse events (CVAEs) associated with sipuleucel-T remain poorly understood. Methods This retrospective, pharmacovigilance analysis used case safety reports from the FDA Adverse Event Reporting System (FAERS) spanning April 2010 to March 2025. Reporting odds ratio (ROR) and information component (IC) were applied to identify and evaluate potential CVAEs associated with sipuleucel-T. Kaplan–Meier method and Weibull distribution were used to analyze reported time-to-onset patterns of sipuleucel-T-related CVAEs. Multivariate logistic regression was employed to explore risk factors for CVAEs following sipuleucel-T treatment. Results Among 4,797 sipuleucel-T-related reports, 743 (15.49%) documented CVAEs, of which 427 (57.5%) were classified as serious. Positive CVAE signals associated with sipuleucel-T included hypertension, venous thromboembolic events, arterial thromboembolic events, cardiac failure, cardiac arrhythmias, and myocardial infarction. The median time to onset of sipuleucel-T-related CVAEs was 14 days, with 80.11% occurring within 1 month. Moreover, the median time to onset of fatal CVAEs was significantly later than that of non-fatal CVAEs (22 days vs. 14 days; p = 0.0076). Additionally, age ≥ 75 years, body weight ≥ 75 kg, and concomitant use of ≥5 medications were identified as independent risk factors for sipuleucel-T-related CVAEs ( p < 0.001). Conclusions This study characterizes the clinical spectrum, time-to-onset patterns, and risk factors of sipuleucel-T-associated CVAEs, providing essential pharmacovigilance data for managing patients with mCRPC.