免疫检查点抑制剂相关血栓栓塞事件文献分析

Literature analysis of thromboembolic events caused by immune checkpoint inhibitor

目的:探讨免疫检查点抑制剂(immune checkpoint inhibitor, ICI)致血栓栓塞事件(thromboembolic events, TEEs)的临床特点。方法:检索Pubmed, Embase, Web of Science数据库(截至2023年2月28日),收集ICI致TEEs的病例报告类文献,提取患者相关信息进行描述性统计分析。结果:共纳入相关文献15篇,涉及患者20例,男性14例,女性6例;年龄48~83岁,其中超过60岁者14例;原发疾病以肺癌最多(11例)。20例患者共涉及5个品种的ICI,包括帕博利珠单抗13例、纳武利尤单抗3例、替雷利珠单抗1例,PD-L1抑制剂1例,伊匹木单抗联合纳武利尤单抗2例;17例患者有ICI用药至发生TEEs的时间记录,13例发生在首次用药3个月以内。20例患者发生静脉血栓栓塞7例次,动脉血栓栓塞15例次。经治疗和/或停用ICI等措施,20例患者中11例好转,5例死亡,4例未报告结局。结论:在免疫治疗早期,临床医师和药师应警惕TEEs的发生,并做好相关检查和常规监测,ICI相关TEEs对症治疗后是否重启ICI治疗需谨慎决定。

Objective:To investigate the clinical characteristics of thromboembolic events(TEEs)caused by immune checkpoint inhibitors(ICIs).Methods:The databases of PubMed,Embase,Web of Science(up to February 28,2023)were searched and the case reports on thromboembolic events caused by ICIs were collected.The relevant information of patients was collected and analyzed descriptively.Results:A total of 15 relevant literature were included,involving 20 patients,14 males and 6 females,aged 48~83 years,of whom 14 were more than 60 years old.The primary diseases were lung cancer in 1l cases.The 20 patients involved five ICIs,including pembrolizumab 13 cases,nivolumab 3 case,tislelizumab 1 case,PD-L1 inhibitor 1 case and ipilimumab combined with nivolumab 2 cases.Of the 20 patients,venous thromboembolism(VTE)occurred for 7 cases and arterial thromboembolism(ATE)for 15 cases.Seventeen patients had a record of the time from the beginning of ICIs treatment to the occurrence of TEEs,most of which occurred within 3 months of medication(13 cases).After treatment and/or withdrawal of ICIs,11 of 20 patients improved,5 died,while 4 did not report the outcome.Conclusion:At the beginning of immunotherapy,clinicians and pharmacists should be vigilant to the occurrence of TEEs,and relevant examination and routine monitoring should be performed.After the symptomatic treatment for ICI-related TEEs,the decision to restart ICI treatment should be made with caution.