Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non‑small-cell lung cancer

Background The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.
Methods This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (≥ 4) and lower NLR (< 4)). PPI use was defined as the administration of PPIs within 30 days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).
Results Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p < 0.01, median OS: 3.3 vs. 19.6 months; p = 0.015). Conversely, in the lower NLR group (n = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3 months, p = 0.83, median OS: 17.6 vs. 24.4 months, p = 0.40).
Conclusion NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s10147-025-02859-2

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