School of General Practice and Continuing Education, Capital Medical University, Beijing, China.
Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
Cancer Med. 2019 May;8(5):2664-2674. doi: 10.1002/cam4.2104. Epub 2019 Apr 5.
Immune-related pneumonitis is a clinically relevant and potentially life-threatening adverse event. We performed a systematic review and network meta-analysis to compare the risk of immune-related pneumonitis among different PD1/PD-L1 inhibitor-related therapeutic regimens.
Randomized controlled trials with PD1/PD-L1 inhibitors were identified through comprehensive searches of multiple databases. Both published and unpublished data were extracted. Bayesian NMA was performed using random-effects models. All-grade (Grade 1-5) and high-grade (Grade 3-5) immune-related pneumonitis were estimated using odds ratios (ORs).
A total of 25 studies involving 16 005 patients were included. Compared with chemotherapy, the ORs of immune-related all-grade and high-grade pneumonitis were significant for nivolumab (all-grade: OR = 6.29, 95% CrI: 2.67-16.75; high-grade: OR = 5.95, 95% CrI: 2.35-17.29), pembrolizumab (all-grade: OR = 5.78, 95% CrI: 2.79-13.24; high-grade: OR = 5.33, 95% CrI: 2.49-12.97), and nivolumab plus ipilimumab therapy (all-grade: OR = 14.82, 95% CrI: 5.48-47.97; high-grade: OR = 15.26, 95% CrI: 5.05-55.52). Compared with nivolumab, nivolumab plus ipilimumab therapy was associated with an increased risk of all-grade pneumonitis (OR = 2.34, 95% CrI: 1.07-5.77). Nivolumab plus ipilimumab therapy had the highest risk of both all-grade and high-grade pneumonitis among PD1/PD-L1 inhibitor-related therapeutic regimens.
This study demonstrates that compared with chemotherapy, PD-1 inhibitor may result in a higher risk of immune-related pneumonitis. Nivolumab plus ipilimumab therapy had the highest pneumonitis risk. These findings could be taken into account by the physicians in decision making.
免疫相关肺炎是一种具有临床相关性且可能危及生命的不良反应。我们进行了一项系统评价和网络荟萃分析，以比较不同 PD1/PD-L1 抑制剂相关治疗方案发生免疫相关肺炎的风险。
通过对多个数据库的全面检索，确定了使用 PD1/PD-L1 抑制剂的随机对照试验。提取已发表和未发表的数据。使用随机效应模型进行贝叶斯网络荟萃分析。使用比值比（ORs）估计所有级别（1-5 级）和高级别（3-5 级）免疫相关肺炎。
共纳入 25 项研究，涉及 16005 例患者。与化疗相比，纳武利尤单抗（所有级别：OR=6.29，95%可信区间：2.67-16.75；高级别：OR=5.95，95%可信区间：2.35-17.29）、帕博利珠单抗（所有级别：OR=5.78，95%可信区间：2.79-13.24；高级别：OR=5.33，95%可信区间：2.49-12.97）和纳武利尤单抗联合伊匹单抗治疗（所有级别：OR=14.82，95%可信区间：5.48-47.97；高级别：OR=15.26，95%可信区间：5.05-55.52）发生所有级别和高级别免疫相关肺炎的 OR 显著升高。与纳武利尤单抗相比，纳武利尤单抗联合伊匹单抗治疗与所有级别肺炎风险增加相关（OR=2.34，95%可信区间：1.07-5.77）。在 PD1/PD-L1 抑制剂相关治疗方案中，纳武利尤单抗联合伊匹单抗治疗具有发生所有级别和高级别肺炎的最高风险。
本研究表明，与化疗相比，PD-1 抑制剂可能会增加免疫相关肺炎的风险。纳武利尤单抗联合伊匹单抗治疗的肺炎风险最高。这些发现可在决策时供医生参考。
