Biomarker ID’d for Response to Anti-Melanoma Biologic – Examination of T cells may predict who will benefit from Keytruda

Source: MedPageToday, September 2015

Two separate studies have identified changes in T-cell subsets before and after treatment with the anti-PD-1 antibody, pembrolizumab (Keytruda), that are predictive of treatment response, new research indicated.

The findings suggest that these changes, detected in peripheral blood cell testing, may help predict which patients with metastatic melanoma are likely to respond to anti-PD-1 therapy and those who will not, according to presentations at at the inaugural International Cancer Immunotherapy Conference in New York City, a program of the American Association for Cancer Research.

Alexander Huang, MD, clinical fellow at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues found that treatment with pembrolizumab invigorated CD8 T-cells among other immune indices, upregulating granzyme B and Ki67 in key CD8 T-cell subsets in blood taken from 39 patients with metastatic melanoma.

The protein granzyme B is a marker of the killing capacity of a CD8-positive T-cell while the protein Ki67 is a marker of cell proliferation. An early increase in granzyme B plus Ki67-positive cells translates into a later increase in granzyme B positive cells, suggesting an early wave of proliferation giving rise to a pool of re-invigorated CD8 T-cells.

“Our goal was to examine immunologic changes that occurred when patients with melanoma were treated with pembrolizumab in an easily accessible body tissue, the blood," Huang said in a statement. “And we were excited to see clear changes in the functional characteristics of CD8-positive T-cells indicative of reinvigoration."

Investigators collected peripheral blood at serial time points before and after pembrolizumab therapy on 39 consecutive patients with stage IV melanoma.

They subsequently analyzed changes in T-cell subsets and differentiation using flow cytometry. Those that express markers of exhaustion including T-bet, Eomes, and inhibitory receptors may represent populations that are invigorated by anti-PD1 therapy.