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Background: Prognosis of patients with metastatic melanoma has improved due to the advent of antibodies targeting the programmed cell death protein-1 (PD-1). However, therapeutic outcomes from anti-PD-1 therapy widely differ among patients. Biomarkers for outcome are needed as these may influence patient selection and treatment decision. Methods: Data of patients with metastatic melanoma treated with anti-PD-1 were retrospectively reviewed. Baseline biochemical (serum lactate dehydrogenase [LDH] levels, complete blood count) and clinical characteristics were evaluated to identify predictors of progression-free survival (PFS) and overall survival (OS). PFS and OS were assessed using Kaplan-Meier and Cox models. The comparison of predictive power of independent predictors for response to anti-PD-1 was evaluated by receiver operating characteristic (ROC) curves. Results: Overall, 173 patients were included. Low metastases burden, normal baseline LDH levels, and high relative lymphocyte count (RLC) were associated with favorable outcomes ( p < 0.01). According to ROC curves, RLC >17.5% improved survival outcomes. PFS was 3.7 and 15.8 months for patients with RLC 17.5%, respectively ( p = 0.004); OS was 5.0 and 33.6 months for patients with RLC 17.5%, respectively ( p < 0.001). Stratification of patients according to these variables showed that survival outcomes strongly differ in patients with 3 of 3 compared to those with 2, 1, and none of these 3 factors present ( p < 0.001). Conclusions: Metastases burden, LDH levels, and RLC are independent baseline characteristics associated with outcome in patients with melanoma receiving anti-PD-1. Further investigations are needed to clarify if evaluation of these parameters can translate into clinical strategy and apply to patient selection.

Purpose Combination therapy with dabrafenib and trametinib is safer and more effective than BRAF inhibitor-based monotherapy for metastatic melanoma. Methods We retrospectively analyzed BRAF-mutated metastatic melanoma patients treated at our institution with daily oral dabrafenib 300 mg and trametinib 2 mg from November 2013 to April 2016. This clinical record included both untreated and previously treated stage IV melanomas. Physical examination and laboratory examinations were performed monthly and disease re-evaluations were performed every 3 months. Results A total of 48 patients (24 male, 24 female) with BRAF-mutated metastatic melanoma received dabrafenib and trametinib; median age was 48 years (range 23-75). Median follow-up was 362.5 days (range 72-879). Best overall response rate consisted of 6.2% (3 patients) complete response, 64.6% (31) partial response, and 25% ( 12 ) stable disease; median time to best response was 11 weeks (range 5.7-125.5). Progression of disease was seen in 19 patients (39.6%), with median time to progression (TTP) of 26 weeks (range 8-54). A total of 15 patients (31.2%) died due to progression of disease. Median progression-free survival and median overall survival were not reached. To date, 30 patients (62.5%) are still under treatment. A total of 27 (56.2%) patients had at least one adverse event (AE); grade 3-4 AEs were seen in 4 cases (8.3%). The main toxicities were fever (25%), skin rash (14.6%), arthralgias (10.4%), and aspartate aminotransferase/alanine aminotransferase increase (8.3%). Treatment dose was reduced in 7 subjects (14.6%), with only one case of discontinuation due to AE. Conclusions Our data, using combined targeted therapy, are in line with the scientific literature in terms of both safety and effectiveness in a real-life setting.