Triple Therapy Found Effective in Patients With Merkel Cell Carcinoma

A new triple therapy approach using a checkpoint inhibitor and T-cell therapy is showing considerable promise in the treatment of Merkel cell carcinoma. In addition, this novel strategy has potential for treating a host of other solid tumors, according to researchers at Fred Hutchinson Cancer Research Center in Seattle.

In a poster that will be presented (abstract 3044) June 5 at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, the research team reported on the use of T-cell therapy combined with avelumab and either radiation or interferon. In two related phase I/II studies, the researchers examined the safety and efficacy of ex vivo expanded Merkel cell polyomavirus (MCPyV)-specific T cells plus human leukocyte antigen upregulation (radiation or interferon) with and without avelumab.

They found that adding the checkpoint inhibitor made a significant difference and kept the cancer at bay in three out of four patients with metastatic Merkel cell carcinoma. The three patients have been in complete remission following treatment.

Study investigator Kelly Paulson, MD, PhD, who will present the findings at the meeting, said this triple therapy approach is like building a campfire. “We’ve got the tumor and we upregulate [a certain protein] to throw some kindling on, and then we put the T cells in to light the match, and then we put the checkpoint blocker in to fan the flames,” said Paulson, who is an oncology fellow at Fred Hutchinson Cancer Center.

This small study of four patients built off a previous study that tested a double combination of just T-cell therapy and radiation or interferon in four patients. The patients did not fare well, and three of them saw their cancer progress and two have since died.

In the current study, the addition of avelumab appeared to kick the T cells into high gear, according to Paulson. The researchers found that the immune cells traveled from the bloodstream to the tumors. In addition, the cells stayed at the tumor sites for months, even when the tumors were no longer clinically detectable. The researchers have followed the patients for a median of 12 months.

All four patients who received triple therapy (100%) are alive and experienced objective responses (RECIST 1.1) with three of four sustained complete responses (CRs) at last follow-up. This compared favorably to outcomes among the four patients who received double therapy (three with progression and one CR [25%] for 14 months before progression). The researchers found that the transferred T cells persisted and peak frequencies correlated with rate of tumor regression in patients receiving triple therapy.

No unexpected side effects were found with the triple therapy. As the researchers expected, patients experienced lymphopenia and cytokine release syndrome. Both were transient. The team found no grade 3/4 toxicities associated with avelumab.