Impact of preexisting interstitial lung disease on pneumonitis and survival during first-line immune checkpoint inhibitor-based therapy in non-small cell lung cancer

BACKGROUND: Evidence remains limited regarding first-line immune checkpoint inhibitor (ICI)-based therapy in patients with non-small cell lung cancer (NSCLC) and preexisting interstitial lung disease (ILD). We evaluated pneumonitis risk and survival based on preexisting ILD status and explored risk stratification in patients with ILD. METHODS: This multicenter retrospective cohort study included 1340 patients with advanced or recurrent NSCLC receiving first-line ICI-based therapy at 15 Japanese institutions between 2017 and 2022. Preexisting ILD and high-resolution computed tomography (HRCT) patterns were centrally reviewed. Pneumonitis and overall survival (OS) were analyzed using Fine-Gray and Cox models. RESULTS: Among 1340 patients, 158 (11.8%) had preexisting ILD. Preexisting ILD was independently associated with higher risks of any-grade pneumonitis (adjusted subdistribution hazard ratio [sHR], 2.64; 95% confidence interval [CI], 1.91-3.65) and grade ≥ 3 pneumonitis (adjusted sHR, 2.18; 95% CI, 1.37-3.47) and with worse OS (adjusted HR, 1.36; 95% CI, 1.12-1.66). Pneumonitis onset was followed by an increased risk of death, particularly for grade ≥ 3 pneumonitis (adjusted HR, 2.25; 95% CI, 1.71-2.96), and its clinical course was poorer in patients with ILD. In patients with ILD, probable usual interstitial pneumonia (UIP)/UIP pattern was associated with higher pneumonitis risk (adjusted sHR, 2.18; 95% CI, 1.27-3.74) and shorter OS (adjusted HR, 2.88; 95% CI, 1.80-4.61). CONCLUSIONS: Among patients receiving first-line ICI-based therapy, preexisting ILD was associated with a higher risk of pneumonitis and shorter survival. In patients with ILD, probable UIP/UIP pattern may identify a subgroup with particularly poor outcomes. Pretreatment HRCT evaluation may therefore be useful for individualized risk-benefit assessment.