PD-1/PD-L1抑制剂在晚期肿瘤患者中的相关肺炎发生率和发生风险:一项荟萃分析

Incidence and Risk of PD-1/PD-L1 Inhibitor-associated Pneumonia in Advance Cancer Patients:A Meta-analysis

背景与目的免疫检查点抑制剂(immune checkpoint inhibitor,ICI)对绝大多数晚期肿瘤具有良好的疗效,给晚期肿瘤患者带来了新的希望,然而由ICI激活的免疫系统,可能攻击人体正常组织器官导致相应的免疫毒性,如ICI相关肺炎。本研究对程序性细胞死亡受体1(programmed cell death protein 1,PD-1)抑制剂及程序性细胞死亡受体配体1(programmed cell death protein ligand 1,PD-L1)抑制剂在晚期肿瘤患者中的相关肺炎发生率和发生风险进行荟萃分析。方法计算机检索PubMed、Cochrane Library、EMbase、中国知网数据库,收集PD-1/PD-L1抑制剂在晚期肿瘤患者中相关肺炎发生率的研究,检索时限为2000年1月-2020年1月。用Revman 5.3软件及R 3.6.2软件进行统计学分析比较不同情况下的肺炎发生率。结果共纳入15篇研究,包含8,642例患者。其中治疗组为PD-1或PD-L1抑制剂,对照组为化疗组,所有级别免疫性肺炎发生率的风险比(odds ratio,OR)为6.63,而高级别为4.87;ICI组非小细胞肺癌中所有级别肺炎发生率是其他瘤种的1.658倍,而高级别肺炎为2.299倍;二线及以上应用ICI所有级别肺炎的发生率是一线的0.489倍,且高级别肺炎的发生率是一线及以上应用ICI的0.449倍。结论与化疗相比,PD-1和PD-L1抑制剂发生相关肺炎的风险较高,在ICI组中非小细胞肺癌以及一线应用中有较高发生风险。本研究为晚期肿瘤的临床治疗用药及并发症防治提供指导依据。

Background and objective Immune checkpoint inhibitors(ICIs)have good efficacy on most advanced tumors,which brings new hope to patients with advanced tumors.However,the immune system activated by ICIs may attack human normal tissues and organs,resulting in corresponding immunotoxicity,such as checkpoint inhibitor pneumonitis.This article carried out a meta-analysis on the incidence and risk of programmed cell death protein 1(PD-1)and programmed cell death protein ligand 1(PD-L1)inhibitor-associated pneumonia in advanced tumors patients.Methods The computer retrieval of PubMed,Cochrane Library,EMbase and CNKI was performed,and the studies on the occurrence rate of PD-1/PD-L1 inhibitor-associated pneumonia in terminal cancer patients were collected,with the retrieval time limit of January 2000 to January 2020.Statistical analysis was conducted by using Revman 5.3 and R 3.6.2 software to compare the occurrence rate of pneumonia under different circumstances.Results 15 studies were included,involving 8,642 patients,of which those with PD-1/PD-L1 inhibitor were treatment group,and those with chemotherapy were control group.The odds radio of all grades of immune pneumonia was 6.63,and that of high grade was 4.87.The occurrence rate of all grades of pneumonia in the ICI group with non-small cell lung cancer(NSCLC)was 1.658 times than other tumors,and that of high grade was 2.299 times.The occurrence rate of all grades of pneumonia in second-line or more treatment with ICI was 0.489 times than that in first-line,and that of high grade was 0.449 times than that in firstline or more treatment with ICI.Conclusion Compared with chemotherapy,the risk of immune-associated pneumonia is higher in PD-1 and PD-L1 inhibitors,and its occurrence risk is high in the ICI group with NSCLC and the first-line treatment with ICI.This paper provides guidance for clinic treatment of terminal cancers and prevention of complications.