Abstract
BackgroundPrevious studies have suggested that elevated neutrophil-to-lymphocyte ratio (NLR) is prognostic for worse outcomes in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors.MethodsThis was a retrospective analysis of 97 consecutive patients with stage IV melanoma who were treated with nivolumab. Baseline NLR and derived (d) NLR were calculated and, along with other characteristics, correlated with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analyses. The best cutoff values for NLR and dNLR were derived using Cutoff Finder software based on an R routine which optimized the significance of the split between Kaplan-Meier survival curves.ResultsIn univariate analysis, increasing absolute neutrophil count (ANC), NLR, dNLR and lactate dehydrogenase (LDH) (continuous variables) were all significantly associated with OS. Only NLR (hazard ratio [HR] = 2.85; 95% CI 1.60–5.08; p < 0.0001) and LDH (HR = 2.51; 95% CI 1.36–4.64; p < 0.0001) maintained a significant association with OS in multivariate analysis. Patients with baseline NLR ≥5 had significantly worse OS and PFS than patients with NLR < 5, as did patients with baseline dNLR ≥3 versus < 3. Optimal cut-off values were ≥ 4.7 for NLR and ≥ 3.8 for dNLR. Using this ≥4.7 cut-off for NLR, the values for OS and PFS were overlapping to the canonical cut-off for values, and dNLR< 3.8 was also associated with better OS and PFS.ConclusionBoth Neutrophil-to-lymphocyte ratio (NLR) and derived (d) NLR were associated with improved survival when baseline levels were lower than cut-off values. NLR and dNLR are simple, inexpensive and readily available biomarkers that could be used to help predict response to immunotherapy in patients with advanced melanoma.
Highlights
Previous studies have suggested that elevated neutrophil-to-lymphocyte ratio (NLR) is prognostic for worse outcomes in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors
Using Harrell’s c-index to determine the prognostic power of NLR and dNLR, we obtained a good prognostic value for both, with c = 0.72 for NLR and c = 0.70 for dNLR
Neutrophilia can occur in cancer patients at a peripheral level, but neutrophils can localize to the tumor due to multiple factors, including general inflammatory signals such as IL-1 and TNF-α [26]
Summary
Previous studies have suggested that elevated neutrophil-to-lymphocyte ratio (NLR) is prognostic for worse outcomes in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors. Improved understanding of cancer and the role of the immune response has resulted in the development of new therapies, including immune checkpoint inhibitors targeting the cytotoxic T-lymphocyte-associated protein (CTLA)-4 (e.g. ipilimumab) and programmed death (PD)-1 receptors (e.g. nivolumab and pembrolizumab). These agents have revolutionized the treatment and outcomes of various cancers, in particular melanoma, with improved long-term disease control and prolonged patient survival [1, 2]. Any such biomarkers should ideally be simple and easy-to-use, inexpensive and readily available
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