Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy

Br J Cancer. 2018 Jul;119(2):193-199. doi: 10.1038/s41416-018-0168-9. Epub 2018 Jul 5.

Abstract

Background: Prescribing anti-programmed death-1 (PD-1) immunotherapy for advanced melanoma is currently not restricted by any biomarker assessment. Determination of programmed death-ligand-1 (PD-L1)-expression status is technically challenging and is not mandatory, because negative tumours also achieve therapeutic responses. However, reproducible biomarkers predictive of a response to anti-PD-1 therapy could contribute to improving therapeutic decision-making.

Methods: This retrospective study on 70 metastatic melanoma patients was undertaken to evaluate the relationships between clinical, histological, immunohistochemical and/or molecular criteria, and the 6-month objective response rate.

Results: Better objective response rates were associated with metachronous metastases (P = 0.04), PD-L1 tumour- and/or immune-cell status (P = 0.01), CD163+ histiocytes at advancing edges (P = 0.009) of primary melanomas and NRAS mutation (P = 0.019). Moreover, CD163+ histiocytes at advancing edges (P = 0.04) were associated with longer progression-free survival (PFS), and metachronous metastases with longer overall survival (P = 0.02) and PFS (P = 0.049).

Conclusions: Combining these reproducible biomarkers could help improve therapeutic decision-making for patients with progressive disease.

MeSH terms

  • Aged
  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / genetics
  • Female
  • GTP Phosphohydrolases / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histiocytes / drug effects
  • Histiocytes / immunology
  • Humans
  • Immunotherapy
  • Male
  • Melanoma / genetics
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / immunology
  • Neoplasms, Second Primary / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Progression-Free Survival
  • Receptors, Cell Surface / genetics*
  • Retrospective Studies

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD163 antigen
  • CD274 protein, human
  • Membrane Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Cell Surface
  • GTP Phosphohydrolases
  • NRAS protein, human