A pharmacovigilance data–driven approach to reveal high fatal adverse events following checkpoint immunotherapy
Abstract
Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of cancer treatment, but they also expose most patients to a variety of treatment-related adverse events (AEs). This study introduces a modified pharmacovigilance approach to identify “ICI-related high-mortality AEs”, a subset of treatment-related complications that are disproportionately reported with elevated fatality during ICI therapy. Utilizing large-scale pharmacovigilance data from 148,972 ICI-treated cases in the FDA AEs Reporting System and 142,645 ICI-treated cases in the WHO global VigiBase, we found 63 types of ICI-related high-mortality AE, such as interstitial lung disease, myositis, and hepatic failure, which necessitate heightened clinical vigilance. Patients who experienced these events had significantly higher fatality reporting rates compared to other cases (36.25% vs. 10.66%). These findings were corroborated in the additional clinical datasets to ensure their generalizability. In summary, identifying these ICI-related high-mortality AEs provides crucial insights for developing proactive monitoring strategies and prioritizes specific events for prevention and intervention to mitigate fatality risk.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Zhen Sun
Xuan Deng
Department of Laboratory Medicine, Huashan Hospital, Fudan University
Jianglong Guo
Mengsi Liu
Guangdong Cardiovascular Institute
Siying Wang
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine
Jian Wang
Jiaojiao Zheng
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine
Kongyan Niu
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine
Weiming Shen
College of Chemistry and Molecular Sciences
Zhen Ye
Chongming Zheng
Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University
Hongye Wang
Department of interventional oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
Fan Yang
Zhouzhou Bao
Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
Kui Ming Chan
Department of Biomedical Sciences, City University of Hong Kong
Gang Chen
Ming Guan
Department of Laboratory Medicine, Huashan Hospital, Fudan University
Haojie Jin
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital