Baseline glucose-to-lymphocyte ratio predicts nivolumab outcomes in advanced non-small cell lung cancer: a multicenter retrospective study

Background: Biomarkers guiding immunotherapy in non-small cell lung cancer (NSCLC) are limited. The glucose-to-lymphocyte ratio (GLR), integrating metabolic and immune status, has shown prognostic value in several cancers but has not been systematically evaluated in patients receiving PD-1 blockade. Methods: We retrospectively analyzed 837 patients with advanced or metastatic NSCLC treated with nivolumab across 21 oncology centers in Turkey (2015-2025). Baseline GLR was calculated from fasting glucose and absolute lymphocyte counts. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier and compared with log-rank tests. Multivariate Cox regression models identified independent predictors. Receiver operating characteristic (ROC) analysis determined the optimal GLR cut-off for OS, which was subsequently applied to PFS analyses for consistency. Results: The optimal GLR cut-off for mortality was ≥70.76 (AUC = 0.635, 95% CI: 0.597-0.674; p < 0.001). Patients with GLR <70.76 achieved significantly longer OS (median 24.1 vs 9.6 months; p < 0.001) and PFS (9.7 vs 5.8 months; p < 0.001) compared with those with GLR ≥70.76. In multivariate analysis, high GLR and poor ECOG performance status independently predicted worse OS. Prior thoracic radiotherapy was associated with improved outcomes. Conclusion: Baseline GLR is a practical, cost-effective biomarker that independently predicts OS in advanced NSCLC patients treated with nivolumab. Elevated GLR likely reflects metabolic dysfunction and impaired immune reserve, both unfavorable for PD-1 blockade efficacy. Prospective studies are warranted to validate GLR and define its role in clinical decision-making.