Metastatic Melanoma Patient Had a Complete Response with Clonal Expansion after Whole Brain Radiation and PD-1 Blockade

Cancer Immunol Res. 2017 Feb;5(2):100-105. doi: 10.1158/2326-6066.CIR-16-0223. Epub 2017 Jan 6.

Abstract

We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy followed by the PD-1-inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8+ T cells in the blood expanded and the ratio of CD8+:Treg T cells increased. A CD8+ T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone. Immunohistochemical analysis confirmed the presence of CD8+ T cells and low PD-L1 expression in the brain metastases before immunotherapy initiation. This sequence of therapy may provide an option for melanoma patients with unresponsive brain metastases. Cancer Immunol Res; 5(2); 100-5. ©2017 AACR.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Clonal Evolution* / genetics
  • Combined Modality Therapy
  • Cranial Irradiation* / methods
  • Female
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Magnetic Resonance Imaging
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Middle Aged
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Biomarkers
  • Programmed Cell Death 1 Receptor
  • pembrolizumab