Impact of Baseline Interstitial Lung Abnormalities on Pneumonitis Risk in Patients Receiving Immune Checkpoint Inhibitors for Non–Small-Cell Lung Cancer

Introduction/Background Immune-related pneumonitis is a potentially fatal complication of treatment with immune checkpoint inhibitors (ICIs). Interstitial lung disease (ILD) is associated with increased risk for pneumonitis, but the impact of interstitial abnormalities (ILA) in the absence of ILD has not been extensively assessed. We examined the relationship between ILA on pretreatment chest computed tomography (CT) scans and risk of pneumonitis in patients with non–small-cell lung cancer (NSCLC). Methods This retrospective cohort study included consecutive adult patients who received ICI for NSCLC between January 2013 and January 2020 at our institution. Two thoracic radiologists blinded to clinical outcomes independently reviewed pre-ICI chest CTs to identify and categorize ILA using previously published definitions. We used uni- and multivariable analysis adjusted for age, radiation, and smoking status to assess for associations between ILA, clinicopathologic characteristics, and symptomatic (CTCAE grade ≥2) pneumonitis. Results Of 475 patients who received ICI treatment and met inclusion criteria, baseline ILA were present in 78 (16.4%) patients, most commonly as a subpleural nonfibrotic pattern. In total, 43 (9.1%) of 475 patients developed symptomatic pneumonitis. Pneumonitis occurred in 16.7% of patients with ILA compared to 7.6% patients without ILA (P < .05). Presence of ground glass and extent of lung parenchymal involvement were associated with an increased risk of pneumonitis. On multivariable analysis, baseline ILA remained associated with increased risk of symptomatic pneumonitis (OR 2.2, 95% CI, 1.0-4.5). Conclusions Baseline ILAs are associated with the development of symptomatic pneumonitis in patients with NSCLC treated with ICI. Additional studies are needed to validate these observations.