Baseline neutrophil-to-lymphocyte ratio and its values monitored over time is associated with outcome of metastatic melanoma patients treated with immunotherapy

Abstract

Background: Neutrophil-to-lymphocyte ratio (N/L) was shown to be prognostic in several solid malignancies. There are limited data about changes of N/L ratios during immunotherapy. The aim of the study was to asses a clinical value of this ratio and its association with tumour response in patients with advanced melanoma. Methods: Between June 2011 and March 2017, 308 patients with metastatic/unresectable melanoma were included to the analysis. Patients age was 58.4±17.3 years (mean), 43 cases had brain metastases. BRAF mutation was present in 107 cases, and 98 patients with positive mutation received targeted therapies with BRAF+/- MEK followed by ipilumumab and/or anti-PD1 therapy. Patients with BRAF negative mutation received immunotherapy (pembrolizumab or nivolumab with/without ipilimumab). In all patients the N/L ratio was assessed at the baseline and monitored during treatment until disease progression or last observation. The cut off for ratio N/L was set at 3. Logistic GEE and Kaplan-Meier survival probability estimation were used for analysis. Results: N/L ratio ≥3 at baseline was significantly associated with poorer overall survival (OS) (p<0.001 in log-rank test). Median overall survival time was 25.8 months (95%CI 20.4-31.2) for N/L ratio <3 vs. 14.0 months (95%CI 10.7-17.3) for N/L ratio ≥3. In repeated measurements analysis, increased N/L ratio was significantly associated the confirmed disease progression, both in univariate random effect model (p<0.001) and multivariate model adjusted for age, gender, presence of BRAF mutation and LDH>URL (p<0.001). N/L ratio in all 6 patient who had pseudo-progression on immunotherapy was not elevated over time. Conclusions: Our results confirm the usefulness of N/L ratio as a prognostic and predictive marker in patients with metastatic melanoma, and monitoring of the N/L ratio over immunotherapy may be helpful for assessment of the disease progression, response, as well as pseudoprogression, thus likely contributes to an optimization of treatment and resource allocation in patients with metastatic melanoma.