Background: Immunotherapy (IO) has changed the disease course of metastatic malignant melanoma (mMM). Prognostic biomarkers are lacking, but high neutrophil-lymphocyte ratio (NLR) has been correlated with poor outcome. Lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR) are also readily available. This study aimed to investigate the prognostic value of NLR, LMR and PLR. Methods: Retrospective cohort of mMM patients (pts) treated with anti PD-1 blockade in 2 centers, between Jan ’13-Aug ’18. Baseline and 6-week (6 w) blood counts were collected. Cut-offs for NLR, LMR and PLR were defined based on literature and ROC curve method. Progression free survival (PFS; primary outcome) and overall survival (OS) were calculated using log rank test. Uni and multivariate analysis were performed using cox-regression model. Results: Baseline characteristics: 83 pts with median age 65.5 years (range 21-90), 77% BRAFwt, 98% PS-ECOG 0-1, 51% LDH >ULN, 5% on steroids. Median NLR 2.7 (IQR 2.1-3.8), LMR 3.1 (2.1-4.3) and PLR 160.8 (98.3-216.4). The majority of pts (65%) were treated with pembrolizumab. With a median follow-up of 6.2 months (m), median PFS was 7.3 m (CI 5.5-9.2) and median OS was 15.9 m (13.4-18.4). In the multivariate model, baseline NLR^high (≥3.0) and PLR^high (≥180.0) were associated with worse PFS (HR 2.04, CI 1.11-3.77; p=0.02; and HR 2.50, CI 1.37-4.57; p=0.003). Baseline LMR^high (≤2.1) was associated with worse PFS (HR 1.886, CI 1.019-3.488; p=0.043) only on the univariate analysis. At 6 w, 16 out of 39 pts with baseline NLR^high presented a decrease in NLR. This was associated with better PFS (HR 0.24, CI 0.09-0.62; p=0.003). Inversely, an increase ≥20% in NLR or PLR was associated with progression (HR 3.65, CI 1.99-6.72, p < 0.001; and HR 3.99, CI 2.01-7.91, p < 0.001). Conclusions: Our data showed that NLR and PLR, as surrogates for systemic inflammation, might be used as prognostic biomarkers for melanoma patients treated with IO. Decreasing NLR in pts with previously high NLR, has a 76% risk reduction of progression. In clinically challenging situations, these biomarkers may help the clinician in an earlier therapeutic orientation.