Risk Factors for Pneumonitis in Patients with Unresectable Advanced Non-small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Abstract

Objective Immune checkpoint inhibitors (ICIs) have become a standard treatment for various cancers; however, they can sometimes induce immune-related adverse events (irAEs). Although pneumonitis during ICI therapy is a critical irAE, the risk factors for pneumonitis remain unclear. This study aimed to evaluate the predictive factors for pneumonitis in patients with non-small cell lung cancer (NSCLC) treated with ICIs.

Methods We conducted a retrospective study of 403 patients with unresectable advanced NSCLC who underwent immune checkpoint inhibitor therapy between January 1, 2016, and January 31, 2024.

Results Among these 403 patients, pneumonitis occurred in 64 (15.9%), including grade ≥3 pneumonitis in 13 (3.2%). The cumulative incidence of pneumonitis differed significantly according to the presence of pre-existing pulmonary disease and was highest in patients with pre-existing idiopathic interstitial pneumonia (IIP). All three cases of grade 5 pneumonitis occurred in patients with IIP without a honeycomb lung. In a multivariate Fine-Gray analysis, pre-existing IIP was independently associated with pneumonitis, whereas honeycomb lung was not associated with pneumonitis development or severity.

Conclusion Pre-existing IIP was independently associated with pneumonitis during immune checkpoint inhibitor therapy. Therefore, baseline lung involvement, particularly pre-existing IIP, should be carefully evaluated before initiating immune checkpoint inhibitor therapy.