Data_Sheet_1_Risk of Pneumonitis and Pneumonia Associated With Immune Checkpoint Inhibitors for Solid Tumors: A Systematic Review and Meta-Analysis.docx (1.42 MB)

Data_Sheet_1_Risk of Pneumonitis and Pneumonia Associated With Immune Checkpoint Inhibitors for Solid Tumors: A Systematic Review and Meta-Analysis.docx

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posted on 04.02.2019, 04:06 by Qiang Su, Emily C. Zhu, Jing-bo Wu, Teng Li, Yan-li Hou, Di-ya Wang, Zu-hua Gao

Background: 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.

Methods: 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.

Results: Among 3,436 studies, 23 randomized clinical trials (RCTs) met our selection criteria which included data from 12,876 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, p < 0.001; RR, 4.14, 95% CI: 1.82–9.42, p < 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, p < 0.001; RR, 2.11, 95% CI: 1.20–3.70, p < 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, p < 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, p < 0.001; RR 3.48, 95%CI: 1.10–11.02, p < 0.001).

Conclusions: 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.

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