Efficacy and safety of immune checkpoint inhibitors in advanced non-small cell lung cancer with idiopathic interstitial pneumonia or interstitial lung abnormalities: NJLCG2301.

Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC). However, their efficacy and safety in patients with idiopathic interstitial pneumonias (IIPs) or interstitial lung abnormalities (ILAs) remain poorly defined, as such patients have been largely excluded from pivotal clinical trials. This study aimed to assess real-world outcomes and adverse events associated with ICI-based therapies in patients with NSCLC and coexisting IIPs or ILAs. Methods: We conducted a multicenter retrospective cohort study across 11 institutions affiliated with the North Japan Lung Cancer Study Group. Patients with advanced NSCLC and pre-existing IIPs or ILAs who received ICI monotherapy or ICI plus chemotherapy (chemo-ICI) between December 2015 and March 2020 were included. Data on progression-free survival (PFS), overall survival (OS), treatment response, and pneumonitis incidence were collected. High-resolution computed tomography (HRCT) images were centrally reviewed to classify the radiologic patterns of IIPs and ILAs. Results: A total of 53 patients with IIPs and 18 with ILAs were analyzed. In the IIP cohort, the median PFS was 5.1 months with chemo-ICI, 7.3 months with first-line ICI monotherapy, and 5.7 months with second-line or later ICI monotherapy. The median OS ranged from 5.4 to 15.4 months, depending on the treatment type. Grade 3-4 pneumonitis occurred in 17.0% of patients with IIPs. In the ILA cohort, chemo-ICI resulted in a median OS of 27.0 months with no cases of pneumonitis, while ICI monotherapy was associated with a 22.2% pneumonitis incidence. Subpleural fibrotic ILAs were linked to a higher risk of pneumonitis. Long-term survivors were identified in both cohorts. Conclusions: ICI therapy may provide durable survival benefits for patients with NSCLC and underlying IIPs or ILAs. However, the elevated incidence of high-grade pneumonitis-particularly in patients with IIPs or fibrotic ILAs-underscores the importance of careful patient selection. Prospective studies are needed to refine treatment strategies in this population.