Consequential administration of intralesional (intratumoral) GM-CSF and IL-2 in the management of metastatic and primary invasive cutaneous melanoma.

Abstract

e20052 Background: Patients with dermal and subdermal metatases as well as invasive primary melanoma allow a great opportunity to evaluate the local and systemic response to intralesional therapy. Methods: Ten patients were studied and completed 2½ years of of follow-up. Four had multiple small intransit metastases each measured 3mm-1cm with 3 to >100 lesions per patient, three had large coalesced sclerotic lesions, and two had distant metastases with palpable subcutaneous nodules. Each received intralesional GM-CSF 500 μg weekly, and in case of failure, IL-2 was substituted at 18 million IU weekly. One patient with invasive primary melanoma and a satellite lesion received both cytokines at the skin lesions one week preoperatively. All the patients had flow cytometric analysis of the peripheral blood before and during therapy. All resected tissues were examined histopathologically and by immunohistochemistry. Results: This was safe and nontoxic program. Three of the four patints with small lesions had complete response (CR) to GM-CSF and one failed but had CR to IL-2. All four patients are alive free of disease for 31-45 months. The three patients with sclerotic lesions failed to respond to either agents. One of the two patients with distant metastases had CR for 6 months. The resected tissues from the patient with primary and satellite lesions revealed complete tumor necrosis with massive histiocytosis and overexpression of CD8+, CD83+ and CD25+ cells at the injection sites and regional lymph nodes and is alive free of disease for over 32 months. The flow cytometric analysis showed no significant changes in white cell differentiation and no dendritic cells were identified before or during therapy. Conclusions: Consequential intralesional administration of GM-CSF and IL-2 seems to have a role in the management of some high-risk patients. While GM-CSF can stimulate autologous dendritic cells, IL-2 activates T cells in the presence of patient own tumor. Such combination can activate a strong antitumor response specific to the patient, which is taken-up by the lymphatics.