Myelodysplastic Syndrome/Acute Myeloid Leukemia Following the Use of Poly-ADP Ribose Polymerase (PARP) Inhibitors: A Real-World Analysis of Postmarketing Surveillance Data

作者全名："Zhao, Quanfeng; Ma, Pan; Fu, Peishu; Wang, Jiayu; Wang, Kejing; Chen, Lin; Yang, Yang"

作者地址："[Zhao, Quanfeng; Ma, Pan; Fu, Peishu] First Affiliated Hosp Third Mil Med Univ, Army Med Univ, Dept Pharm, Chongqing, Peoples R China; [Wang, Jiayu; Wang, Kejing; Chen, Lin; Yang, Yang] Women & Childrens Hosp Chongqing Med Univ, Dept Pharm, Chongqing, Peoples R China; [Wang, Jiayu; Wang, Kejing; Chen, Lin; Yang, Yang] Chongqing Hlth Ctr Women & Children, Dept Pharm, Chongqing, Peoples R China"

通信作者："Wang, KJ; Chen, L; Yang, Y (通讯作者)，Women & Childrens Hosp Chongqing Med Univ, Dept Pharm, Chongqing, Peoples R China.; Wang, KJ; Chen, L; Yang, Y (通讯作者)，Chongqing Hlth Ctr Women & Children, Dept Pharm, Chongqing, Peoples R China."

来源：FRONTIERS IN PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000817844100001

JCR分区：Q1

影响因子：5.6

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：PARP inhibitors; myelodysplastic syndrome; acute myeloid leukemia; pharmacovigilance; real-world

摘要："Background and purpose: poly-ADP ribose polymerase (PARP) inhibitors show impressive efficacy in a range of tumors. However, concerns about rare and fatal adverse events, including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have arisen. The aim of this study was to excavate and evaluate the risk of PARP inhibitors causing MDS and AML based on real-world data from two international pharmacovigilance databases.Methods: We analyzed adverse event (AE) reports of four PARP inhibitors (olaparib, niraparib, rucaparib and talazoparib) associated with MDS and AML from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and EudraVigilance (EV) databases between 1 October 2014, and 30 September 2021, including demographic characteristics, fatality and times to onset. Three different data mining algorithms were used to detect the signals of PARP inhibitors associated with MDS and AML.Results: In total, 16,710 and 11,937 PARP inhibitor AE reports were found in the FAERS and EV databases, of which 332 and 349 were associated with MDS and AML, respectively. The median latencies of MDS and AML associated with PARP inhibitors were 211 [interquartile range (IQR) 93.5-491.25] days and 355 (IQR 72.00-483.50) days, respectively. The average fatality rates of MDS and AML caused by the four PARP inhibitors were 37.96 and 60.41%, respectively, in the FAERS database, while those in the EV database were 5.83 and 12.16%, respectively. Based on the criteria used for the three algorithms, a significant disproportionate association was found between PARP inhibitors as a drug class and MDS/AML. Notably, the risk of MDS was much higher than that of AML. Olaparib appeared to have a stronger association with MDS and AML than did other PARP inhibitors.Conclusion: In the real world, PARP inhibitors increase the risk of MDS and AML, which can result in high mortality and tend to occur during long-term use. Our findings provide objective evidence for the postmarketing safety of PARP inhibitors."

基金机构："Natural Science Foundation Project of Chongqing Health Center for Women and Children [2020YJQN04, 2021YJMS07]; Chongqing Clinical Pharmacy Key Specialties Construction Project"

基金资助正文：Natural Science Foundation Project of Chongqing Health Center for Women and Children (2020YJQN04 and 2021YJMS07). Chongqing Clinical Pharmacy Key Specialties Construction Project.