Granulocyte-macrophage colony stimulating factor (GM-CSF) & Interleukin-2 (IL-2) combination as adjuvant therapy in cutaneous melanoma. Early results of a phase II clinical trial

Abstract

7559 Background: GM-CSF leads to dendritic cell priming and activation, and also increases IL-2 receptor expression on T-lymphocytes. IL-2 creates LAK cells and TIL cells. Therefore, it was compelling to combine these 2 agents, each with a different function but a complimentary action. Methods: This is an open label, single arm study. 16 patients participated and underwent potentially curative surgery. Post-operatively, each patient received GM-CSF: 125μgm/m2/day, sc ×14 days; followed by IL-2: 9 million IU/m2/day, sc ×4 days, then 10 –12 days of no treatment. This cycle was repeated once/month for 6 months, i.e., 6 cycles. In addition, patients with large tumors received autologous melanoma vaccine. All the patients were observed, and in the event of recurrence or metastases, the patient was evaluated for resection and was re-treated on the same program. Results: The patient population consisted of: 8 patients with T3b-T4b primary melanoma. The remaining 8 patients had metastases to regional lymph nodes (LN), iliac LN ± intransit metastases, and resected distant metastases. 6 patients had large enough tumors that yielded sufficient tumor cells and received autologous tumor vaccine with the biotherapy. This program was well tolerated with minimal complaints, and good patient compliance. 9 patients developed WBC >20,000/cmm with a high eosinophil count. 2 patients developed subcutaneous nodules away from any site of GM-CSF or IL-2 injections. Pathology proved these to be LN packed with T lymphocytes and a few foci of β cells. Fifteen patients are alive free of disease (including 2 who were re-treated) after 6–26 months of follow-up (median 14). Conclusions: 1. In an attempt to intensify this therapy without increasing the dosage (because of the leucocytosis) we plan to extend this treatment to one year. 2. It seems that surgical resection of recurrences and metastases followed by Biotherapy or Bio-Immunotherapy can be an effective approach in the management of this disease. No significant financial relationships to disclose.