Developing a score system to predict therapeutic outcomes to anti-PD-1 immunotherapy in metastatic melanoma.

Abstract

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. 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. 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% and >17.5%, respectively (p = 0.004); OS was 5.0 and 33.6 months for patients with RLC <17.5% and >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). 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.