Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab

BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced non-small cell lung cancer (NSCLC); however, there is no well-established prognostic biomarker. We investigated the relationship between survival outcomes and three peripheral blood biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), as well as a new score termed the risk blood biomarker (RBB), calculated from the combination of the neutrophil-monocyte-to-lymphocyte ratio (NMLR) and white blood cell count (WBC). METHODS: This study included patients with stage IV or recurrent NSCLC confirmed with programmed death ligand 1 (PD-L1) expression ≥50% who received pembrolizumab monotherapy as first-line treatment at the Virgen del Rocío University Hospital in Seville, Spain. To establish the relationship between baseline peripheral blood biomarkers and survival outcomes, progression free survival (PFS) and overall survival (OS), we used the Kaplan-Meier method and multivariable Cox regression models. RESULTS: A total of 51 patients were included in this study. In multivariate analysis, baseline NLR and PLR showed a strong association with PFS [NLR hazard ratio (HR): 0.19, 95% confidence interval (CI): 0.09–0.44, P<0.001; PLR HR: 0.46, 95% CI: 0.23–0.92, P=0.03] and OS (NLR HR: 0.07, 95% CI: 0.02–0.19, P<0.001; PLR HR: 0.29, 95% CI: 0.13–0.67, P=0.004), and the MLR was associated with OS (MLR HR: 0.34, 95% CI: 0.15–0.76, P=0.01). According to the RBB score, groups with lower scores were associated with superior PFS (group 0: HR: 0.16, 95% CI: 0.06–0.41, P<0.001 and group 1: HR: 0.29, 95% CI: 0.12–0.73, P=0.01) and OS (group 0: HR: 0.04, 95% CI: 0.01–0.17, P<0.001 and group 1: HR: 0.15, 95% CI: 0.05–0.42, P<0.001). CONCLUSIONS: Low baseline NLR, MLR and PLR are significantly associated with better PFS, and low baseline NLR and PLR are associated with better OS. Additionally, we identified three subgroups of patients using the RBB score, and low scores were associated with improved survival outcomes and response to therapy.