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Combining Interleukin-2 With Imiquimod and Topical Retinoid Therapy May Be Effective Against Cutaneous Metastatic Melanoma

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Key Points

  • About 10% of patients with advanced melanoma develop cutaneous metastases, often located “in transit” to the patients’ lymph nodes.
  • All patients in the study achieved complete clinical response to the treated lesions within 1 to 3 months of starting the intralesional interleukin-2–based therapy.
  • After 2 years, 82% of patients were alive, and seven were alive without melanoma recurrence at the conclusion of the study.

A novel combination therapy appears to be effective in treating patients with melanoma skin metastases, according to new research from the University of California (UC) Davis. Led by Emanual Maverakis, MD, of the UC Davis Department of Dermatology, the research found that interleukin-2 combined with imiquimod and topical retinoid therapy in patients with so-called in-transit metastases is a promising therapeutic option.

The findings were published by Shi et al in the Journal of the American Academy of Dermatology.

Cutaneous Metastatic Melanoma

“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 to the skin,” said Dr. Maverakis, 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 interleukin-2 has recently been included in the National Comprehensive Cancer Network (NCCN) Guidelines for management of melanoma metastases of the skin, U.S. physicians have not yet adopted it, according to the researchers.

About 10% 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 recurrence can still be very high.

Study Findings

The researchers conducted a retrospective analysis of patients with either stage III or stage IV melanoma who had a history of treatment with interleukin-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, with comorbidities. Of the 11 patients, 10 had experienced recurrences of the disease after surgery, and nonsurgical treatments had failed in several as well.

The data indicated that all patients achieved complete clinical response to the treated lesions within 1 to 3 months of starting the intralesional interleukin-2–based therapy. After 2 years, 82% of patients were alive, and seven were alive without melanoma recurrence at the conclusion of the study. The remaining five patients died of unrelated causes.

“The favorable outcomes in these patients are encouraging and suggest that the therapeutic regimen may have a survival benefit,” concluded Dr. Maverakis and the research team.

The authors noted 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.

Dr. Maverakis is the corresponding author of the Journal of the American Academy of Dermatology article.

The study was supported by the Burroughs Wellcome Fund, the Howard Hughes Medical Institute, and the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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