ACTIVE SPECIFIC IMMUNOTHERAPY OF METASTATIC MELANOMA WITH AN ANTIIDIOTYPE VACCINE - A PHASE I II TRIAL OF I-MEL-2 PLUS SAF-M/

Purpose: To determine the toxicity and immunologic activity of on anti idiotype melanoma vaccine that consists of monoclonal antibody I-Mel-2 (MELIMMUNE-5, IDEC Pharmaceuticals, La Jolla, CA) and an immunologic adjuvant SAF-m. Patients and Methods: Twenty-six patients with metasta tic melanoma, whom had previously received chemotherapy, were given 2 mg of I-Mel-2 and either 100 mu g (n=6) or 250 mu g (n=20) of SAF-m. A ntiidiotype vaccine was given intramuscularly (IM) biweekly for 4 week s, and then bimonthly until disease progression. Human antimurine anti bodies (HAMA), anti-I-Mel-2 antibodies, and specific antibody (Ab)3 ag ainst the melanoma epitope mimicked by the vaccine were titrated befor e treatment, biweekly from weeks 4 to 12, and every 4 to 8 weeks there after. Computed tomographic (CT) scans of the chest, abdomen, and pelv is and magnetic resonance imaging (MRI) of the brain were obtained bef ore and bimonthly during treatment to evaluate responses. Results: Ele vated titers of human antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical antitumor effect (P=.02 and P=.05, resp ectively). Ab3 wets absent in most patients, but was found in the best clinical responder. Fever, myalgias/arthralgias, fatigue, nausea, and headaches were the most common toxicities. Grade III myalgias/arthral gias and headaches required dose reduction of SAF-m in eight patients at the 250-mu g dose. No treatment-related death occurred. Six patient s had an antitumor effect: one complete response in liver and lung, tw o minor responses, and three stable disease. The patient with a comple te response has survived nearly 5 years. Conclusion: I-Mel-2 antiidiot ype vaccine was safe, tolerated best the 100-mu g dose of SAF-m, and h ad immunologic and clinical activity. (C) 1997 by American Society of Clinical Oncology.