Prognostic implications of adverse events associated with CAR-T cell therapy: a population-based global observational study

作者：Zhen Sun, Jianglong Guo, Mengsi Liu, Hongye Wang, Zhe Li, Weiming Shen, Siying Wang, Huijue Zhu, Xiaoye Liu, Jinhao Li, Yuan Ouyang, Yueze Zhu, Zhen Ye, Shunpeng Xing, Gang Chen, Haojie Jin · 发表于：EClinicalMedicine · 年份：2025 · DOI：10.1016/j.eclinm.2025.103623 · 被引用次数：2 · 研究领域：CAR-T cell therapy research、Biomedical Ethics and Regulation、Safe Handling of Antineoplastic Drugs

Background: Chimeric antigen receptor (CAR)-T cell therapy offers a promising and transformative treatment option for patients with hematologic malignancies, with expanding potential in solid tumors and non-malignant diseases. However, it also exposes recipients to a wide spectrum of treatment-related toxicities, complicating its clinical implementation. The limited sample sizes of clinical studies hinder a comprehensive understanding of how different adverse events (AEs) may impact CAR-T treatment outcomes. Methods: Based on two global real-world drug safety surveillance systems, this observational pharmacovigilance study identified safety signals and death-related AEs in CAR-T cell therapy. All consecutive CAR-T cell-treated cases with AEs reported to the World Health Organization' VigiBase (as of March 2025) and U.S. Food and Drug Administration Adverse Event Reporting System (as of June 2024) were included. We evaluated disproportionate risk and death of all reported AEs by the modified reporting odds ratio method. AE fatality rates, reporting odds ratio of fatality rates among different AEs, and CAR-T cell therapy safety signals were reported. Findings: This analysis included 12,511 CAR-T cell-treated cases in FAERS from 37 countries/regions, 2861 had a fatal outcome. Disproportionality analysis identified 266 AEs as safety signals associated with CAR-T therapy. Of these, 59 high-fatality AEs were revealed (average fatality rate 49.35% [189/383]), such as pulmonary hemor...