Dynamics of clinical biomarkers as predictors of immunotherapy benefit in metastatic melanoma patients

Clin Transl Oncol. 2021 Feb;23(2):311-317. doi: 10.1007/s12094-020-02420-9. Epub 2020 Jun 19.

Abstract

Purpose: Baseline LDH, derived neutrophil-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) are associated with outcomes of patients with metastatic melanoma (MM). We hypothesized whether dynamic shifts in LDH, dNLR and incidence of irAEs may impact the prognosis of MM patients treated with anti-CTLA4 or anti-PD1 as single agents.

Methods: Retrospective analysis of medical charts from MM patients with prospective monitoring of dNLR, LDH values and irAE incidence. Primary endpoint was overall survival (OS).

Results: Patients switching from either high dNLR (≥2.5) to low dNLR (HR: 0.14; 0.03-0.74; p = 0.02) or high LDH (≥1.5 × ULN) to low LDH levels (HR: 0.08; 0.01-0.68; p = 0.02) had significantly better OS than those with high dNLR or LDH scores at the end of cycle 2. Longer OS was also observed in patients developing irAEs ≥ grade 2 as compared to no irAEs (HR: 0.2; 0.05-0.89; p = 0.03).

Conclusions: We found that major shifts in dNLR and LDH measures from baseline to cycle 2 measures and shifts from baseline to cycle 2 are significantly associated with OS in MM patients receiving single agent anti-PD1 therapy. Laboratory changes and clinical variables may help optimize prognostic estimates.

Keywords: Anti-PD1; Biomarkers; Melanoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers, Tumor / blood*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / adverse effects
  • Ipilimumab / therapeutic use
  • Lactate Dehydrogenases / blood*
  • Lymphocytes / cytology*
  • Male
  • Melanoma / blood
  • Melanoma / mortality*
  • Melanoma / secondary
  • Melanoma / therapy
  • Middle Aged
  • Neutrophils / cytology*
  • Nivolumab / therapeutic use
  • Prospective Studies
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Ipilimumab
  • Nivolumab
  • pembrolizumab
  • Lactate Dehydrogenases