Immune-related Pneumonitis Associated with Immune Checkpoint Inhibitors in Lung Cancer: a Network Meta-analysis

Background: Immune checkpoint inhibitors (ICIs) have dramatically revolutionized lung cancer treatment, providing unprecedented clinical benefits. However, immune-related pneumonitis (IRP) caused by ICIs has aroused widespread concern due to its high rate of discontinuation and mortality. This network meta-analysis (NMA) aims to compare the risks of IRP among different regimens for advanced lung cancer.

Methods: Phase II and III randomized clinical trials (RCTs) were searched from electronic databases. The rates of grade 1-5 IRP and grade 3-5 IRP were systematically extracted. An NMA was conducted among chemotherapy, ICIs monotherapy, dual ICIs combination, and ICIs+chemotherapy. Subgroup analysis was also compared based on specific types of ICIs.

Results: Twenty-five RCTs involving 17,310 patients were eligible for inclusion. Compared with chemotherapy, ICI-based regimens were associated with an increased risk of grade 1-5 IRP and grade 3-5 IRP. Compared with ICIs+chemotherapy, ICIs monotherapy (grade 1-5: OR 2.14, 95% credible interval 1.12 to 4.80; grade 3-5: 3.03, 1.491 to 6.69) and dual ICIs combination (grade 1-5: 3.86, 1.69 to 9.89; grade 3-5: 5.12, 2.01 to 13.68) were associated with a higher risk of grade 1-5 IRP and grade 3-5 IRP. No significant difference was found between dual ICIs combination and ICIs monotherapy in grade 1-5 IRP (1.85, 0.91 to 3.37) or in grade 3-5 IRP (1.65, 0.81 to 3.37). Besides, compared with programmed cell death protein 1 (PD-1) inhibitors (2.56, 1.12 to 6.60), a lower risk of grade 1-5 IRP was observed in programmed cell death ligand 1 (PD-L1) inhibitors.

Conclusion: Compared with chemotherapy, using ICIs is associated with an increased risk of IRP. ICIs+chemotherapy is associated with a lower risk of IRP compared with dual ICIs combination and ICIs monotherapy. PD-1 inhibitors are associated with a higher risk of 1-5 grade IRP compared with PD-L1 inhibitors.