In findings never before seen in melanoma, a novel combination therapy was found to be highly effective at treating patients with skin metastases, new research from UC Davis has shown.
Led by Emanual Maverakis of the UC Davis Department of Dermatology, the research found that Interleukin (IL)-2 combined with imiquimod and topical retinoid therapy in patients with so-called “in-transit metastases” is a promising therapeutic option.
The findings have been published online first in the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2015.06.060).
“It’s unclear if the recently developed targeted melanoma therapies that have revolutionized management of patients with internal melanoma metastases are useful in patients with metastatic disease limited of the skin,” said Maverakis, who is an associate professor of dermatology. “Our results demonstrate that intralesional therapy with a protein that causes immune cells to divide, given in combination with a topically applied immune activator, can be a highly effective treatment for these patients.”
Although intralesional IL-2 has recently been included in the U.S. National Comprehensive Cancer Network guidelines for management of melanoma metastases of the skin, U.S. physicians have not adopted it, according to the researchers.
About 10 percent of patients with advanced melanoma develop what are called cutaneous metastases, often located “in-transit” to the patients’ lymph nodes. Historically, treatment for these metastatic lesions has been surgical excision with or without radiation therapy, but disease recurrences can still be very high.
For the study, the researchers did a retrospective analysis of patients with either stage III or stage IV melanoma who had history of treatment with IL-2 therapy combined with imiquimod and a topical retinoid. The patients had been seen by the dermatology service between 2006 and 2015; most were elderly and had other illnesses. Ten of the 11 patients had experienced recurrences of the disease after surgery, and several had failed non-surgical treatments, as well.
The data indicated that all patients achieved complete clinical response to the treated lesions within one to three months of starting the intralesional IL-2-based therapy. After two years, 82 percent of patients were alive, and seven were alive at the conclusion of the study without melanoma recurrence. The remaining five patients died from unrelated causes.
“The favorable outcomes in these patients are encouraging and suggest that the therapeutic regimen may have a survival benefit,” concluded Maverakis and the research team.
The authors note that the study has limitations in that the records of only 11 patients were analyzed, and there were no experiments conducted to determine the effects of the therapeutic regimen on the systemic immune response.
Other study authors were Vivian Y. Shi, Khiem Tran, Forum Patel, Jonathan Leventhal, Thomas Konia, Maxwell A. Fung, Reason Wilken, Miki Shirakawa Garcia, Sarah D. Fitzmaurice, Jayne Joo, Arta M. Monjazeb, Barbara A. Burrall, Brett King, Steve Martinez and Scott D. Christensen.
Funding for the study came from Burroughs Wellcome Fund, Howard Hughes Medical Institute and the National Institutes of Health (grant #DP2OD008752).