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

Abstract

Background: Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced nonsmall 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 neutrophilto-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.

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Correlation of preclinical and clinical biomarkers with efficacy and toxicity of cancer immunotherapy

“… 72 Other studies constructed risk blood biomarkers by combining white blood cell count and NLR. 73 Meanwhile, high eosinophil count (⩾1.5%) and relative lymphocyte count (⩾17.5%) were proved to be independent baseline characteristics associated with longer OS in melanoma patients treated with pembrolizumab. 74 Kiriu et al 75 found that patients with PsP have significantly lower NLR than patients with true tumor progression before and after treatment.…”

Comparative Analysis of Predictive Biomarkers for PD-1/PD-L1 Inhibitors in Cancers: Developments and Challenges

“…It has been reported that IFN-γ–related gene expression signatures constructed with 10 genes or 28 genes are able to predict the response to pembrolizumab in patients with metastatic melanoma [ 179 ]. In the CheckMate 275 and KEYNOTE-028 trials, higher scores of the 25-gene or 6-gene IFN-γ signature were demonstrated to be associated with a better immunotherapy response in urothelial and esophageal carcinomas [ 19 , 180 ]. The exploratory analyses from the POPLAR trial revealed that high T-effector-IFN-γ–associated gene expression predicted an OS benefit from atezolizumab over docetaxel, whereas in patients with low T-effector-IFN-γ–associated gene expression, there was no significant difference in OS between those treated with atezolizumab or docetaxel [ 35 ].…”

“…High relative eosinophil counts (≥1.5%) and relative lymphocyte counts (≥17.5%) were demonstrated to be independent baseline characteristics that were correlated with longer OS in melanoma patients treated with pembrolizumab [ 121 ]. A new score, termed the risk blood biomarker, is calculated by combining the white blood cell count and neutrophil-monocyte-to-lymphocyte ratio, and was associated with a better survival and response to immunotherapy [ 180 ]. Elevated pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were independently associated with poorer OS and PFS and lower response rates in NSCLC patients treated with nivolumab [ 122 ].…”