Immune checkpoint inhibitor-associated interstitial lung diseases correlate with better prognosis in patients with advanced non-small-cell lung cancer

Abstract

Background: Interstitial lung disease (ILD) induced by immune checkpoint inhibitors (ICIs) is a potentially life-threatening adverse event. The purpose of this study was to evaluate whether the development of immune-related adverse events (irAEs), especially ILD, was associated with treatment efficacy and to research the features and risk factors of ILD in advanced non-small cell lung cancer (NSCLC).

Methods: Between December 2015 and November 2018, 130 advanced NSCLC patients were treated with nivolumab, pembrolizumab or atezolizumab. The patients were categorized into two groups (irAEs group or non-irAEs group). Subsequently, we divided the irAEs group into two groups based on the incidence of ILD (ILD group and irAEs-non-ILD group). Treatment efficacy and the characteristics of ILD were evaluated.

Results: A total of 39 (30%) patients developed irAEs. ILD was observed in 16 (12%) patients. Patients with ILD had a higher objective response rate (ORR) compared with irAEs-non-ILD patients and non-irAEs patients (63%, 43% and 22%, respectively). Median progression-free survival (mPFS) was 15.9 months in ILD patients, 5.4 months in irAEs-non-ILD patients and 3.3 months in non-irAEs patients (log-rank test, P = 0.033). Pre-existing interstitial pneumonia (IP) was an independent risk factor for ILD-induced ICIs (odds ratio [OR] 14.7; 95% confidence interval [CI]: 2.16-99.6, P = 0.006).

Conclusions: ORR and PFS were significantly better in ILD patients than in irAEs-non-ILD and non-irAEs patients. Pre-existing history of IP was an independent risk factor for ILD-induced ICIs.

Keywords: Immune check inhibitor; immune-related adverse events; interstitial lung disease; prognosis.