Risk of immune-related pneumonitis for PD1/PD-L1 inhibitors: Systematic review and network meta-analysis

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 Both published and unpublished data were extracted.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.