Severe Immune-related Adverse Events and Their Effect on Survival in Patients With Advanced Non–small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors

Background/Aim: Immune checkpoint inhibitors (ICIs) have become central in the treatment of non-small cell lung cancer (NSCLC). The occurrence of immune-related adverse events (irAEs) is a critical issue in the management of patients with NSCLC receiving ICIs. Recent studies have suggested that patients who develop irAEs may have a better prognosis than those who do not. However, the most problematic cases involved the development of severe irAEs. This study aimed to investigate the clinical impact of severe irAEs (grade ≥3) in patients with NSCLC treated with ICIs. Patients and Methods: We analyzed 122 patients from a prospective database of consecutive patients with NSCLC who received first-line ICI-containing treatment between November 2018 and October 2024. Patients were classified into two groups: 48 treated with anti-programmed death-ligand 1 (anti-PD-L1) therapy and 74 treated with anti-programmed death-1 (anti-PD-1) therapy. We retrospectively compared the incidence of severe irAEs between the two groups and evaluated the clinical outcomes of severe irAEs on the survival. Results: Among 122 patients, 24 (19.7%) experienced severe irAEs. The incidence of severe irAEs was significantly higher among patients treated with anti-PD-1 than among those treated with anti-PD-L1. The incidence of irAE-related death was also higher in the anti-PD-1 group than in the anti-PD-L1 group, with pneumonitis accounting for most of these fatalities (87.5%). There were no significant differences in the progression-free or overall survival between patients with and without severe irAEs. A multivariable analysis showed that the use of anti-PD-1 therapy was associated with a worse overall survival. Conclusion: Treatment with anti-PD-1 was associated with an increased risk of severe irAEs. The incidence of severe irAEs was not associated with an improved survival rate.