Vascular and neurological toxicity profile of Sipuleucel-T: a large-scale real world pharmacovigilance study

Background: As the first FDA-approved autologous cellular immunotherapy, Sipuleucel-T requires comprehensive safety evaluation, particularly regarding its neurological and cardiovascular adverse effects. Methods: This study analyzed adverse event signals associated with Sipuleucel-T using the FDA Adverse Event Reporting System (FAERS) database from 2010 to 2024, employing reporting odds ratio (ROR) methodology and logistic regression analysis. Adverse drug reaction (ADR) signals were considered significant when the number of reports exceeded 3 and the lower limit of ROR (95% CI) was greater than 1. The analysis focused on associations between the target drug and both Preferred Terms (PT) and System Organ Classes (SOC). Results: Analysis of the FAERS database (n = 47,894,299) revealed Sipuleucel-T (n = 12,948) has no significant overall association with neurological system disorders (ROR = 0.98[0.92-1.04]), but showed significant risks for specific events: cerebrovascular accident (ROR = 2.09), transient ischemic attack (ROR = 5.03), Guillain-Barré syndrome (ROR = 3.22), and cardiovascular events including atrial fibrillation (ROR = 3.38), acute myocardial infarction (ROR = 5.08), and deep vein thrombosis (ROR = 5.18). Regression analysis demonstrated increased cerebrovascular risk in patients aged 70-80 years (OR = 3.55), while higher body weight (>90 kg) served as a protective factor (OR = 0.30). Cerebrovascular events exhibited a bimodal distribution, with 44.3% occurring after 6 months, suggesting potential long-term immunomodulatory effects. Conclusion: The neurological toxicity of Sipuleucel-T is relatively modest. Age (70-80 years) and body weight were identified as independent predictors of cerebrovascular events during treatment, with higher body weight showing a protective effect. This study identifies high-risk population characteristics for Sipuleucel-T-associated cerebrovascular events, providing important data to support clinical safety measures.