免疫检查点抑制剂治疗晚期肺癌毒副反应临床观察  

Clinical observation of side effect of immune checkpoint inhibitors in treatment of advanced lung cancer

作　　者：王露方 江丰收 贾伟[1] 王玲玉 张志红 王伟[1] 王刚[1] 韩兴华 孙玉蓓 王勇[1] 潘跃银 WANG Lu-fang;JIANG Feng-shou;JIA Wei;WANG Ling-yu;ZHANG Zhi-hong;WANG Wei;WANG Gang;HAN Xing-hua;SUN Yu-bei;WANG Yong;PAN Yue-yin(Department of oncology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui 230001,China)

机构地区：[1]中国科学技术大学附属第一医院肿瘤化疗科,安徽合肥230001

出　　处：《临床肺科杂志》2020年第9期1389-1394,共6页Journal of Clinical Pulmonary Medicine

基　　金：中国科学技术大学附属第一医院(安徽省立医院)“登峰计划”学科建设项目(No﹝2019﹞17号)。

摘　　要：目的免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)是抗肿瘤治疗里程碑式事件之一,随着ICIs的临床应用,这类药物所导致的免疫相关性毒副反应(immune-related adverse events,irAEs)也带来了很多挑战。研究观察ICIs在晚期肺癌患者治疗中各系统毒性反应。方法回顾性分析2018年9月至2020年2月在中国科学技术大学附属第一医院治疗的43例晚期肺癌患者,在接受Pembrolizumab和Nivolumab治疗后的毒副反应。结果IrAEs发生率≥25%的毒副反应,包括:疲劳、食欲减弱、恶心、白细胞(White blood cell,WBC)减少、中性粒细胞(Neutrophils)减少、贫血(Anemia)、谷氨酰转肽酶(Glutamyltranspeptidase,GGT)升高、瘙痒。极少数表现3~5级副反应:疲劳、恶心、食欲减弱、肌酐(Creatinine,CREA)升高、心肺毒性,两药发生率无差异(P>0.05)。1例患者表现为4级心脏毒性,频发心律失常,以频发房颤为主,伴有贫血、口腔溃疡、肾功能损害,诱发脑梗死,永久停用ICIs治疗。结论免疫检查点抑制剂治疗晚期肺癌,总体安全性较好,但是需要警惕罕见致命毒性反应。Objective Immune checkpoint inhibitors(ICIs)have made marvelous breakthroughs in carcinoma treatment.However,the widely use of ICIs is associated with a series of immune-related adverse events(irAEs),which leads to a great challenge.In this article,we have summarized irAEs in advanced lung cancer.Methods Patients with advanced lung cancer who were treated with ICIs in the First Affiliated Hospital of USTC were retrospectively analyzed from September 2018 to February 2020.Results The clinical date of 43 patients with advanced lung cancer confirmed by histology were treated with pembrolizumab and nivolumab.The main side effects of irAEs were asthenia,anorexia,nausea,leucopenia,neutropenia,anemia,GGT increase and pruritus.The incidence of irAEs was less than 10%,mainly including transfusion reaction,diarrhea,oral ulcer,TBIL increase,CREA increase,occult blood,hyperthyroidism,hypothyroidism,cardiotoxicity and pulmonary toxicity.Most of the patients had grade 1~2 toxic reactions,while few of them had grade 3~5 toxic reactions,such as asthenia,nausea,anorexia,CREA increase,cardiotoxicity and pulmonary toxicity.There was no significant difference in the incidence of side effects between the two ICIs(P>0.05).One patient could not tolerate the side effects of ICIs,mainly manifested as grade 4 cardiotoxicity,frequent atrial fibrillation,anemia,oral ulcer,renal function damage,cerebral infarction,so the treatment of ICIs was stopped permanently.Conclusion Immune checkpoint inhibitors are safe in treatment of advanced lung cancer,but it is necessary to guard against rare and fatal side effects.

关 键 词：肺肿瘤 免疫检查点抑制剂 罕见致命毒性反应 心脏毒性反应 

分 类 号：R734.2[医药卫生—肿瘤]