The efficacy of anti-programmed cell death protein 1 therapy among patients with metastatic acral and metastatic mucosal melanoma

Cancer Med. 2021 Apr;10(7):2293-2299. doi: 10.1002/cam4.3781. Epub 2021 Mar 8.

Abstract

Background: Anti-programmed cell death protein 1 (PD-1) antibodies are a standard treatment for metastatic melanoma patients. However, the understanding of the efficacy of anti-PD-1 for acral melanoma (AM) and mucosal melanoma (MM) is limited as these subtypes are relatively rare compared to cutaneous melanoma (CM).

Methods: This single institution, retrospective cohort study included patients with advanced AM and MM who underwent anti-PD-1 therapy for metastatic melanoma between 2012 and 2018. Objective responses were determined using the investigator-assessed Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method. A Cox regression analysis was performed to identify the factors associated with survival outcomes.

Results: Ninety-seven patients were identified, 38 (39%) with AM and 59 (61%) with MM. The objective response rates (ORRs) were 21.0% and 15.2% in patients with AM and MM, respectively. The median PFS and OS were 3.6 and 25.7 months for AM patients, and 3.0 and 20.1 months for MM patients, respectively. Elevated serum lactate dehydrogenase (LDH) (AM: hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.06-0.87; p = 0.03, MM: HR, 0.20; 95% CI, 0.08-0.53; p = 0.001) was significantly associated with shorter OS for both subtypes.

Conclusions: The ORR, PFS, and OS with anti-PD-1 therapy were poor in patients with AM and MM compared to those previously reported clinical trials for nonacral CM. High serum LDH was associated with significantly shorter OS.

Keywords: acral melanoma; anti-PD-1; malignant melanoma; mucosal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Confidence Intervals
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / blood
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Nivolumab / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Progression-Free Survival
  • Rare Diseases / drug therapy*
  • Rare Diseases / genetics
  • Rare Diseases / mortality
  • Rare Diseases / pathology
  • Response Evaluation Criteria in Solid Tumors
  • Retrospective Studies
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab
  • L-Lactate Dehydrogenase