Fatal pneumonitis associated with immune checkpoint inhibitors: a study based on 128 cohorts with 26,994 participants

Abstract Background: With the widespread application of immune checkpoint inhibitors (ICIs), the immune-related adverse events (irAEs) were increasingly reported. Checkpoint inhibitor pneumonitis (CIP) was a frequent irAE with high mortality. Hence it is crucial to estimate the frequency and susceptible factors of fatal CIP.Methods: PubMed, Embase and Cochrane Library were searched for relevant studies that assessed fatal CIP. Primary endpoints were the incidence and susceptible factors of fatal CIP.Results: A total of 173 cases of fatal CIP occurred in 128 cohorts. The overall incidence was 0.96% [95% confidence interval (CI): 0.80-1.14%]. The odds and incidence were remarkably higher in hematologic malignancy group (compared with solid tumors) [3.86 vs. 0.90, odds ratio (OR): 2.41, 95% CI: 1.10-5.28, P=0.028], and in ≥2 line treatment group (compared with first line treatment group) [1.29 vs. 0.74, OR: 1.76, 95% CI: 1.24-2.44, P=0.001]. Meanwhile, the frequency was significantly decreased in phase Ⅲ trial group (compared with that of phase Ⅰ/Ⅱ trial group) [ 0.56 vs. 1.69 , OR: 0.37, 95% CI: 0.26-0.53, P＜0.0001].Conclusions: The overall incidence of fatal CIP was 0.96%. The susceptible factors of fatal CIP were hematologic malignancy, phase Ⅰ/Ⅱ trial, and ≥2 line treatment group. The study provided a capability for clinicians to predict and discriminate high-risk populations of fatal CIP.