Metastatic melanoma: positron emission tomographic (PET)/computed tomography (CT) images. A-C, PET/CT of the head and neck after recurrence of malignant melanoma reveals increased FDG uptake spanning from the nose, left malar cheek, to the left ear, which represents a large melanoma (8.5 cm) and multiple additional in-transit metastases. E-G, Three months after restarting intralesional interleukin 2, imiquimod, and a topical retinoid, there is resolution of the enhancing lesions. D, At initial presentation, PET/CT image (patient 8) shows increased FDG uptake in the skin and subcutaneous tissues of the back of right forearm, consistent with biopsy-proven melanoma (18- × 6-cm plaque). H, At 5 months posttreatment, no hypermetabolic lesion is identified. Creit: 10.1016/j.jaad.2015.06.060
Led by Emanual Maverakis of the UC Davis Department of Dermatology, the research found that Interleukin IL2 combined with imiquimod and topical retinoid therapy in patients with so-called “in-transit metastases” is a promising therapeutic option. “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.”
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 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. Ten of the 11 patients had experienced recurrences of the disease after surgery, and several had failed non-surgical treatments, as well.
Cutaneous melanoma: clinical and histologic comparisons before and after treatment with intralesional interleukin 2 in combination with topical imiquimod and a retinoid cream. A and B, Before treatment, a large melanoma encompassing most of the right forearm of an 89-year-old man (patient 8). This same arm during (C) and 31 months after (D) immunotherapy, demonstrating a depigmented arm. Biopsy specimens of this site reveal some residual pigment within melanophages but no active melanoma. E, Hematoxylin-eosin staining of a biopsy specimen taken before initiation of immunotherapy (patient 5) reveals numerous atypical melanocytes within the dermis. These melanocytes have prominent nucleoli (thin arrow) and an increased nuclear to cytoplasmic ratio (broad arrow). (Original magnification: ×400.) F, A posttreatment biopsy specimen from the same patient reveals the absence of atypical melanocytes and the presence of melanophages (arrow) within a background of fibrin necrosis and degenerated collagen. A mixed infiltrate with neutrophils, histiocytes, and lymphocytes is also seen. Dusky melanin pigment is present within the melanophages (arrow). G, Melan-A staining of the biopsy specimen (shown in F) fails to detect atypical melanocytes. Credit: 10.1016/j.jaad.2015.06.060
The data indicated that all patients achieved complete clinical response to the treated lesions within 1 -3 months of starting the intralesional IL-2-based therapy. After 2 years, 82% of patients were alive, and 7 were alive at the conclusion of the study without melanoma recurrence. The remaining 5 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. http://www.newswise.com/articles/new-combination-treatment-effective-against-melanoma-skin-metastases
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