血液系统恶性肿瘤中 CAR-T 细胞疗法相关感染：真实世界药物警戒分析

Chimeric antigen receptor T-cell therapy-related adverse events have become a focus of clinical attention.

However, a comprehensive study of infection-related adverse events remains scarce, especially for high-risk, life-threatening infections. To provide real-world evidence from a pharmacovigilance perspective for monitoring infection-related adverse events.

This study investigated the characteristics of infection-related adverse events using the Food and Drug Administration Adverse Event Reporting System database. The disproportionality analysis was used to calculate the reporting odds ratios of infections. Time to onset (TTO) and outcomes were analyzed to describe the temporal distribution and severity of infections. The least absolute shrinkage and selection operator (LASSO) regression was used to screen death-associated infections. The co-occurrence analysis was utilized to investigate the mechanism of infection occurrence. A total of 2142 reports of infection-related adverse events were obtained, accounting for 17. 6% of total reports. At the high-level term (HLT) level, 31 positive safety signals were identified, including 12 bacterial infections, 12 viral infections, 4 fungal infections, 2 organ-specific infections, and 1 other infection.

The median TTO of infections was 6 d (interquartile range: 2 to 24). The HLT-level positive signals with death proportions exceeding 50% predominantly pertained to sepsis-related infections, fungal infections, and Gram-negative bacterial infections. The LASSO analysis further demonstrated that those infections were associated with fatal outcomes.

The co-occurrence analysis indicated that infections were associated with immune dysregulation. The prevalence, early onset, and broad spectrum of infection-related adverse events necessitate clinical attention. High-risk infections, including sepsis-related infections, fungal infections, and Gram-negative bacterial infections, especially warrant heightened vigilance.