Biomarker Tied to Immunotherapy Response in Melanoma

Researchers at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, have identified a potential biomarker in patients with stage IV melanoma being treated with the immunotherapy pembrolizumab.

Since being approved for the treatment of metastatic melanoma in September 2014, many patients have demonstrated remarkable and durable responses to treatment with pembrolizumab; however, the majority does not. Therefore, in a presentation at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (Sept 25-28, 2016; New York, NY), researchers set out to investigate whether the ratio of specific immune cells in the blood of patients with melanoma correlated with tumor burden and clinical response.
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In the study, researchers analyzed blood samples from 29 patients with stage IV melanoma taken three, six, nine, and twelve weeks after starting treatment with pembrolizumab.  They found that, over time, immune cells called CD8+ T became increasingly more dysfunctional as they battled cancer.

"Exhausted-phenotype CD8+ T cells have high levels of the protein PD-1 on their surface. Pembrolizumab targets PD-1. In preclinical models, pembrolizumab targeting of PD-1 can reinvigorate exhausted-phenotype CD8+ T cells, something that we can measure by increased levels of proliferation markers like Ki67," said Alexander Huang, MD, University of Pennsylvania.

They found that there was increased proliferation of exhausted phenotype CD8+T cells in 78% of patients post treatment. Further, 38% of patients experienced a clinical response, as measured by the immune-related RECIST criteria. And in a cohort of patients with a clinical response exceeding 1.94, the entire group was alive at 11-months after receiving treatment with pembrolizumab.

“We were excited to find that patients with a balance in favor of the immune response compared to tumor burden were more likely to have clinical benefit,” said Dr Huang. “If validated in larger studies, this could provide a way to predict early on after starting pembrolizumab treatment whether a patient should continue this treatment or either change to a different treatment or add an additional treatment.