Risk of immune checkpoint inhibitor–related pneumonitis in non-small cell lung cancer patients with chronic obstructive pulmonary disease: A propensity score–matched analysis.

Abstract

e20596 Background: Immune checkpoint inhibitors (ICIs) are standard therapy for non-small cell lung cancer (NSCLC) but can cause immune-related pneumonitis. Patients with chronic obstructive pulmonary disease (COPD) may be at increased risk, though real-world data are limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network to identify adults with NSCLC who initiated ICI therapy between 2015-2022. Patients were stratified by COPD status. Exclusion criteria include secondary malignancies, autoimmune disease, or pre-existing pneumonitis. Propensity score matching (1:1) was performed based on age, sex, race, ethnicity, comorbidities (hypertension, ischemic heart disease, cerebrovascular disease, chronic kidney disease), and prior radiation therapy. The primary outcome was pneumonitis within 2 years of ICI initiation. Secondary outcomes included all-cause mortality, all-cause hospitalization, and ICU admission. Results: Before matching, 3,234 patients with COPD and 5,967 patients without COPD were identified. After propensity score matching, 2,914 patients were included in each cohort. Baseline characteristics and comorbid conditions were well-balanced between the two cohorts: mean age 73 years, 55% male, hypertension (51%), ischemic heart disease (21%), cerebrovascular disease (12%), and chronic kidney disease (11%). Pneumonitis occurred in 8.6% (n = 251) of patients with COPD versus 4.2% (n = 122) without COPD. COPD was associated with significantly increased risk of pneumonitis (HR 1.88, 95% CI 1.51-2.33; log-rank p<0.001). All-cause mortality and hospitalization rates were similar between cohorts; however, ICU admission was more common in patients with COPD (9.4% vs 6.0%; hazard ratio 1.44, 95% CI 1.19–1.75; p < 0.001). Conclusions: Among patients with NSCLC treated with ICIs, pre-existing COPD was associated with nearly 2-fold increased risk of pneumonitis. These findings highlight the need for enhanced monitoring and risk-stratified management of patients with COPD receiving immunotherapy.