Impact of immune-related adverse events on clinical outcomes in patients with advanced non-small cell lung cancer with low PD-L1 expression, focusing on pneumonitis: a multicenter retrospective study in Japan

Background: Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC. Methods: We retrospectively enrolled 850 patients with programmed cell death ligand-1 (PD-L1) 1–49% advanced NSCLC who were treated with chemotherapy alone or with combined immunotherapy and chemotherapy as first-line treatment at 19 different institutions in Japan between March 2017 and June 2022. Using data from their medical records, we examined the type and severity of irAEs and their association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS). Results: OS and PFS were not significantly different between patients with and without severe irAEs. However, in the group receiving combined immunotherapy and chemotherapy, those who developed pneumonitis within 42 days of treatment initiation had shorter OS and PFS, irrespective of the pneumonitis grade, and a worse prognosis than those who received chemotherapy alone. Additionally, early-onset pneumonitis was more likely in patients aged >75 years, those with high lactate dehydrogenase levels, and those receiving steroids or immunosuppressants, suggesting that these factors may contribute to the risk of early-onset pneumonitis. Conclusions: Early-onset pneumonitis is a poor prognostic factor in patients with PD-L1 1–49% advanced NSCLC receiving combined immunotherapy and chemotherapy. Further large-scale observational studies are warranted to confirm these findings.