Sun You-Meng, Li Wei, Chen Zhi-Yu, Wang Ying
The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
School of Statistics and Mathematics, Zhejiang Gongshang University, Hangzhou, China.
Front Oncol. 2021 Oct 21;11:651553. doi: 10.3389/fonc.2021.651553. eCollection 2021.
Immune checkpoint inhibitors (ICIs) have dramatically altered the treatment landscape for patients with melanoma. However, their use also generates unique immune-related adverse effects (irAEs). We performed a systematic review and network meta-analysis to compare the risk of pneumonitis associated with ICIs for patients with advanced or metastatic melanoma.
Phase II/III randomized clinical trials (RCTs) with ICIs were identified through comprehensive searches of multiple databases. An NMA was conducted to compare the risk of pneumonitis associated with ICIs and all-grade (grade 1-5) and high-grade (grade 3-5) immune-related pneumonitis (IRP) were estimated by odds ratios (ORs).
A total of 10 randomized clinical trials involving 5,335 patients were enrolled in this study. Conventional chemotherapy was associated with a lower risk of grade 1-5 IRP compared with ICIs monotherapy (OR, 0.14, 95% CI, 0.03 to 0.73) and dual ICIs combination (OR, 0.03, 95% CI, 0.00 to 0.19). In addition, dual ICIs combination showed a noticeably higher risk than ICI monotherapy (OR, 4.45, 95% CI, 2.14 to 9.25) of grade 1-5 IRP. No significant difference in grade 1-5 IRP was observed between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors. As to grade 3-5 IRP, no statistically significant difference was found among different ICIs-based regimens.
These findings revealed that ICIs could increase the risk of all-grade pneumonitis for patients with advanced melanoma, compared with conventional chemotherapy. Dual ICIs combination could further increase the risk of all-grade pneumonitis than ICIs monotherapy. There was no significant difference in the risk of pneumonia between CTLA-4 and PD-1 inhibitors.
免疫检查点抑制剂（ICI）显著改变了黑色素瘤患者的治疗格局。然而，其使用也会产生独特的免疫相关不良反应（irAE）。我们进行了一项系统评价和网状Meta分析，以比较晚期或转移性黑色素瘤患者使用ICI相关肺炎的风险。
通过全面检索多个数据库，确定使用ICI的II/III期随机临床试验（RCT）。进行网状Meta分析，比较与ICI相关的肺炎风险，并通过比值比（OR）估计所有级别（1-5级）和高级别（3-5级）免疫相关肺炎（IRP）的风险。
本研究共纳入10项涉及5335例患者的随机临床试验。与ICI单药治疗（OR，0.14，95%CI，0.03至0.73）和双ICI联合治疗（OR，0.03，95%CI，0.00至0.19）相比，传统化疗与1-5级IRP风险较低相关。此外，双ICI联合治疗显示1-5级IRP风险比ICI单药治疗显著更高（OR，4.45，95%CI，2.14至9.25）。在细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性细胞死亡蛋白1（PD-1）抑制剂之间，未观察到1-5级IRP的显著差异。对于3-5级IRP，在不同的基于ICI的治疗方案之间未发现统计学显著差异。
这些发现表明，与传统化疗相比，ICI可增加晚期黑色素瘤患者全级别肺炎的风险。双ICI联合治疗比ICI单药治疗可进一步增加全级别肺炎的风险。CTLA-4和PD-1抑制剂之间的肺炎风险无显著差异。
