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.,This 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.,In 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.,Both 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.,The online version of this article (10.1186/s40425-018-0383-1) contains supplementary material, which is available to authorized users.
Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant.,Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients.,Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified.,NLR was calculated before treatment and at 3-week intervals after treatment initiation until 9 weeks.,Baseline NLR was tested for association with overall survival (OS), progression free survival (PFS), and clinical response to treatment.,On-treatment NLRs were tested for association with the same outcomes using landmark survival analyses and time-dependent Cox regression models.,The association of relative change of NLR from baseline with outcomes was also examined.,A multivariate model tested the association of NLR and OS/PFS with additional clinical factors.,There were 197 IPI patients and 65 BRAFi patients.,In multivariable analysis adjusting for M stage, and disease type (in OS)/gender (in PFS), an NLR value of 5 or above at every timepoint was associated with worse OS (HR 2.03-3.37, p < 0.001), PFS (HR 1.81-2.51, p < 0.001), and response to therapy (OR 3.92-9.18, p < 0.007), in the IPI cohort.,In addition, a > 30% increase in NLR above baseline at any timepoint was associated with a worse OS and PFS (HR 1.81 and 1.66, p < 0.004).,In BRAFi patients, NLR was not consistently associated with outcomes.,A high NLR, whether measured prior to or during treatment with IPI, is associated with worse OS, PFS, and clinical response in patients with advanced melanoma.,An increasing NLR from baseline during treatment was correlated with worse OS and PFS in IPI-treated patients.,In comparison, as NLR was not associated with outcomes in BRAFi patients, NLR may have a uniquely predictive value in patients treated with immunotherapy.,•Neutrophil to lymphocyte ratio is associated with important clinical outcomes in melanoma patients treated with ipilimumab.,•Changes in neutrophil to lymphocyte ratio from baseline during treatment with ipilimumab correlate with clinical outcomes•Neutrophil to lymphocyte ratio is not associated with outcomes in those treated with BRAF inhibitors,Neutrophil to lymphocyte ratio is associated with important clinical outcomes in melanoma patients treated with ipilimumab.,Changes in neutrophil to lymphocyte ratio from baseline during treatment with ipilimumab correlate with clinical outcomes,Neutrophil to lymphocyte ratio is not associated with outcomes in those treated with BRAF inhibitors,Baseline neutrophil to lymphocyte ratio (NLR) and changes in NLR during treatment associate with important clinical outcomes, including overall survival, progression-free survival, and clinical response in advanced melanoma patients treated with immunotherapy, and therefore may have a valuable role in selecting patients most likely or least likely to benefit from treatment, or for monitoring response to treatment over time.,This marker is not useful in patients treated with BRAF inhibitors, perhaps reflecting its unique value in immunotherapy.