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Can a Single Dose of PD-1 Inhibitor Before Surgery Predict Outcomes in Melanoma?

By: Joseph Fanelli
Posted: Monday, April 22, 2019

According to findings presented in Nature Medicine, a single dose of PD-1 inhibitor before resection in patients with melanoma may predict clinical outcomes. Additionally, immune responses brought on by the therapy can peak as early as 7 days after treatment, concluded Alexander C. Huang, MD, of the Perelman School of Medicine at the University of Pennsylvania and the Parker Institute for Cancer Immunotherapy, and colleagues.

“Knowing so much earlier whether or not patients are responding to PD-1 inhibitors may give us the ability to guide them to the most appropriate therapy with the greatest chance for success,” Dr. Huang said in Penn Medicine News.

The study—which included reportedly the largest cohort of patients to be treated with anti–PD-1 agents before surgery—focused on 27 patients with melanoma. They receive a single dose of the PD-1 inhibitor pembrolizumab 3 weeks before surgery.

Researchers identified a rapid antitumor response, with 8 of the 27 patients experiencing a complete or major pathologic response after a single dose of pemrolizumab. All 8 of those patients were disease-free after 2.5-month follow-up. The rapid pathologic and clinical responses were associated with accumulation of exhausted CD8 T cells in the tumor at 3 weeks, with reinvigoration in the blood observed as early as 1 week.

“We’ve now identified patterns in the way the cancer can adapt to survive, meaning we may be able to guess it’s next move after PD-1 treatment,” Dr. Huang added. “The longer into treatment we go, the more mutations and resistance mechanisms we find, but identifying the means of resistance early after starting therapy in resected tumors means the resistance mechanisms may be more predictable, which is another benefit of giving this treatment before surgery.”

Disclosure: The study authors’ disclosure information may be found at nature.com.



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