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Background <p>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.</p> Methods <p>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 (&lt; 4)). PPI use was defined as the administration of PPIs within 30&#xa0;days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).</p> Results <p>Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (<i>n</i> = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2&#xa0;months; <i>p</i> &lt; 0.01, median OS: 3.3 vs. 19.6&#xa0;months; <i>p</i> = 0.015). Conversely, in the lower NLR group (<i>n</i> = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3&#xa0;months, <i>p</i> = 0.83, median OS: 17.6 vs. 24.4&#xa0;months, <i>p</i> = 0.40).</p> Conclusion <p>NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy.</p>

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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

  • 期刊论文

  • 发表日期：

    2025年9月2日

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  • Tomoki Hori,
  • Kazuhiro Yamamoto,
  • Takefumi Ito,
  • Shigeki Ikushima,
  • Tomohiro Omura,
  • Ikuko Yano

摘要

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.