Good results from trial of immunotherapy for Merkel cell carcinoma
April 22, 2016
Multispectral immunofluorescence showing the interface between Merkel cell tumor cells (orange) and host immune cells (yellow marks CD8+ lymphocytes, red marks CD68+ macrophages). Cell-surface PD-L1 expression (green) is observed on macrophages, lymphocytes and tumor cells, adjacent to PD-1 expression (white) on lymphocytes.
Courtesy of Janis Taube, Johns Hopkins.
Results from a clinical trial of the immunotherapy drug pembrolizumab as a treatment for Merkel cell carcinoma show promise, with half of 25 patients experiencing substantial shrinkage of their tumours. That shrinkage lasted an average of three times as long as improvement due to conventional chemotherapy, and some patients had no remaining evidence of disease. The findings come from a paper published online ahead of print in The New England Journal of Medicine (Apr. 19, 2016).
A rare skin cancer often seen on the head and neck, Merkel cell carcinoma has been linked to a virus, Merkel cell polyomavirus. The paper’s authors, researchers from the Fred Hutchinson Cancer Research Center in Seattle and the Johns Hopkins Kimmel Cancer Center in Baltimore, said in a press release that their findings may indicate how patients with virus-associated cancers may respond to immune checkpoint blocker or inhibitor drugs.
“What we found in this preliminary study of patients with Merkel cell cancer may not be true for every virus-induced cancer,” study author Dr. Suzanne Topalian, professor of surgery and oncology and associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, said in the release, “but if additional studies with more patients confirm our findings, we will have strong reason to believe that many cancers with virus-linked proteins could be valid targets for immune checkpoint blockade.”
According to the paper, a total of 26 patients with advanced Merkel cell carcinoma were who had received no previous systemic therapy were enrolled. Each patient received 2 mg/kg of pembrolizumab every three weeks. The primary endpoint was the objective response rate based on the Response Evaluation Criteria in Solid Tumors, version 1.1, and efficacy was correlated with tumour viral status. One patient was not able to be evaluated during the treatment period. Of the remaining 25, the objective response rate was 56% (95% confidence interval [CI], 35 to 76). That included four patients who had a complete response, and 10 who had a partial response. Median follow-up was 33 weeks (range, 7 to 53), and two of the 14 patients who had a response had relapses (14%). The response duration ranged from at least 2.2 months to at least 9.7 months, with a progression-free survival rate at six months of 67% (95% CI, 49 to 86).
According to the authors, Merkel cell carcinomas treated with conventional chemotherapy recur on average after three months. “Compared with traditional chemotherapy, about the same percentage of patients responded to pembrolizumab in this study, but these patients’ responses were longer lasting,” said study author Dr. Evan Lipson, assistant professor at the Johns Hopkins Kimmel Cancer Center, in the release.
Virus-positive tumours occurred in 17 of the 26 patients (65%). The response rate was 62% among patients with Merkel-cell polyomavirus-positive tumours (10 of 16 patients) and 44% among those with virus-negative tumours (four of nine patients).