Checkpoint Inhibitor Pneumonitis in Non‐Small Cell Lung Cancer With Chronic Lung Disease: A Comparative Study of ILD , COPD , and the General Population Using a Global Federated Database

BACKGROUND AND OBJECTIVE: Checkpoint inhibitor pneumonitis (CIP) is a serious immune-related adverse event. Patients with interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD) may be at increased risk, but data comparing these populations is limited. We aimed to evaluate differences in CIP incidence, onset, recurrence, and outcomes among patients with ILD, COPD, and those without pre-existing lung disease. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network, identifying patients who received immune checkpoint inhibitors (ICIs) between January 2017 and January 2023. Patients were stratified into ILD, COPD, and control groups. CIP was identified using ICD codes. Propensity score matching (1:1:1) was used to adjust for baseline characteristics. Outcomes included CIP incidence, time to onset, recurrence, hospitalisation, and mortality. RESULTS: Among 184,000+ ICI recipients, 3147 had ILD, 8657 had COPD, and 47,031 had no known lung disease. After matching (n = 3147/group), CIP incidence was highest in ILD patients (4.6%) compared to COPD (1.9%) and controls (1.5%) (p < 0.001). Time to CIP onset was similar across groups. ILD patients with CIP had higher recurrence (16.4% vs. 9.1% and 8.3%) and higher all-cause hospitalisation (61% vs. 40% and 39%) compared to COPD and control groups. All-cause mortality was also higher in the ILD-CIP group (41.1%). CONCLUSION: ILD significantly increases the risk of developing CIP and worsens associated outcomes, including recurrence and mortality. These findings support closer surveillance and risk stratification in ICI-treated patients with underlying ILD.