Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Desautels Faculty of Management, McGill University, Montreal, QC, Canada.
Front Immunol. 2019 Feb 4;10:108. doi: 10.3389/fimmu.2019.00108. eCollection 2019.
We performed a systematic review and meta-analysis to evaluate the risk of pneumonitis and pneumonia associated with immune checkpoint inhibitors (ICIs) for solid tumors. The following keywords were used in searching the Embase and PubMed database: pneumonitis, pneumonia, and immune checkpoint inhibitors. The data was analyzed by using the R software and Metafor package. Among 3,436 studies, 23 randomized clinical trials (RCTs) met our selection criteria which included data from patients. Compared with chemotherapy, PD-1 inhibitors showed significant increase in grade 1-5 and grade 3-5 pneumonitis (RR, 5.17, 95% CI: 2.82-9.47, < 0.001; RR, 4.14, 95% CI: 1.82-9.42, < 0.001), but not in pneumonia. PD-L1 inhibitors showed significant increase in grade 1-5 pneumonitis and pneumonia (RR, 3.25, 95% CI: 1.61-6.57, < 0.001; RR, 2.11, 95% CI: 1.20-3.70, < 0.001). There was no significant difference in any grade pneumonitis and pneumonia in cytotoxic T lymphocyte-associated protein 4 (CTLA4) inhibitors subgroup. Programmed cell death protein 1 (PD-1) inhibitor (nivolumab and pembrolizumab) both showed significant increase in grade 1-5 pneumonitis, and pembrolizumab specially tended to increase grade 3-5 pneumonitis. (RR, 5.64 95% CI: 1.94-16.38, < 0.001). Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab) monotherapy, PD-1 inhibitor, and CTLA-4 inhibitor (nivolumab plus ipilimumab) combination therapies showed significant increase in grade 1-5 and grade 3-5 pneumonitis (RR 3.47, 95%CI:1.76-6.83, < 0.001; RR 3.48, 95%CI: 1.10-11.02, < 0.001). PD-1/PD-L1 inhibitors treatment could increase the risk of all-grade pneumonitis. CTLA4 inhibitor ipilimumab treatment alone could not increase the risk of pneumonitis but could augment the risk of pneumonitis in PD-1/PD-L1 inhibitor treated patients. There was no significant increase in the risk of pneumonia after either PD-1/PDL-1inhibitor or CTLA4 inhibitor treatment alone or in combination.
我们进行了一项系统评价和荟萃分析，以评估免疫检查点抑制剂（ICI）治疗实体瘤相关肺炎和肺炎的风险。在 Embase 和 PubMed 数据库中使用了以下关键词：肺炎、肺炎和免疫检查点抑制剂。使用 R 软件和 Metafor 包分析数据。在 3436 项研究中，23 项随机临床试验（RCT）符合我们的选择标准，其中包括患者的数据。与化疗相比，PD-1 抑制剂在 1-5 级和 3-5 级肺炎方面显示出显著增加（RR，5.17，95%CI：2.82-9.47，<0.001；RR，4.14，95%CI：1.82-9.42，<0.001），但在肺炎方面没有显著增加。PD-L1 抑制剂在 1-5 级肺炎和肺炎方面显示出显著增加（RR，3.25，95%CI：1.61-6.57，<0.001；RR，2.11，95%CI：1.20-3.70，<0.001）。细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）抑制剂亚组中，任何级别肺炎和肺炎均无显著差异。程序性死亡蛋白 1（PD-1）抑制剂（nivolumab 和 pembrolizumab）均显示 1-5 级肺炎显著增加，pembrolizumab 特别倾向于增加 3-5 级肺炎。（RR，5.64 95%CI：1.94-16.38，<0.001）。与 PD-1 抑制剂（nivolumab）或 CTLA-4 抑制剂（ipilimumab）单药治疗相比，PD-1 抑制剂和 CTLA-4 抑制剂（nivolumab 加 ipilimumab）联合治疗在 1-5 级和 3-5 级肺炎方面显示出显著增加（RR 3.47，95%CI：1.76-6.83，<0.001；RR 3.48，95%CI：1.10-11.02，<0.001）。PD-1/PD-L1 抑制剂治疗可增加全级肺炎的风险。CTLA4 抑制剂 ipilimumab 单独治疗不能增加肺炎的风险，但可增加 PD-1/PD-L1 抑制剂治疗患者肺炎的风险。单独使用 PD-1/PDL-1 抑制剂或 CTLA4 抑制剂或联合治疗均不会增加肺炎的风险。
