Melanoma: single-dose response to PD-1 blockade predicts outcomes

  • Huang AC & al.
  • Nat Med
  • 25 Feb 2019

  • curated by Brian Richardson, PhD
  • Univadis Clinical Summaries
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Takeaway

  • Patient response to a single dose of neoadjuvant anti-PD-1 therapy can be used to predict clinical outcomes of patients with high-risk, resectable stage III/IV melanoma.

Why this matters

  • This study provides important information on the mechanisms of anti-PD-1 therapy in the tumor environment.

Key results

  • 29.6% of patients experienced a complete or major pathological response.
    • All these patients remained disease-free during the study.
  • Increases in exhausted CD8 T cells were observed at day 7 in blood collected from responders and at 3 weeks in their tumor tissue.
  • Analysis of posttreatment tumor revealed a distinct signature of T-cell activation compared with pretreatment.
  • A pretreatment immune signature including genes involved in T-cell activation, adaptive immune response, and T-cell migration correlated with posttreatment response and recurrence-free survival.
  • Patients who experienced recurrence showed low amounts of CD8 T cells and possible mutational escape and tumor evolution.

Study design

  • 27 patients with stage III/IV melanoma were treated with neoadjuvant/adjuvant anti-PD-1 therapy (pembrolizumab) and analyzed for response rates and outcomes.
  • Funding: SPORE in Skin Cancer; NIH/National Cancer Institute; Tara Miler Foundation; Melanoma Research Alliance; David and Hallee Adelman Immunotherapy Research Fund; DFG; Parker Institute for Cancer Immunotherapy; MSD.

Limitations

  • Small patient sample size.