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% 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).
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.
Keywords: LDH; Melanoma; anti-PD-1; immunotherapy; leukocytes; prognosis.