Active specific immunotherapy of metastatic melanoma with an antiidiotype vaccine: a phase I/II trial of I-Mel-2 plus SAF-m.

Abstract

PURPOSE:

To determine the toxicity and immunologic activity of an antiidiotype melanoma vaccine that consists of monoclonal antibody I-Mel-2 (MELIMMUNE-2, IDEC Pharmaceuticals, La Jolla, CA) and an immunologic adjuvant SAF-m.

PATIENTS AND METHODS:

Twenty-six patients with metastatic melanoma, 17 of whom had previously received chemotherapy, were given 2 mg of I-Mel-2 and either 100 micrograms (n = 6) or 250 micrograms (n = 20) of SAF-m. Antiidiotype vaccine was given intramuscularly (IM) biweekly for 4 weeks, and then bimonthly until disease progression. Human antimurine antibodies (HAMA), anti-I-Mel-2 antibodies, and specific antibody (Ab)3 against the melanoma epitope mimicked by the vaccine were titrated before treatment, biweekly from weeks 4 to 12, and every 4 to 8 weeks thereafter. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging (MRI) of the brain were obtained before and bimonthly during treatment to evaluate responses.

RESULTS:

Elevated titers of human antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical antitumor effect (P = .02 and P = .05, respectively). Ab3 was 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/arthralgias and headaches required dose reduction of SAF-m in eight patients at the 250-microgram dose. No treatment-related death occurred. Six patients had an antitumor effect: one complete response in liver and lung, two minor responses, and three stable disease. The patient with a complete response has survived nearly 5 years.

CONCLUSION:

I-Mel-2 antiidiotype vaccine was safe, tolerated best at the 100-microgram dose of SAF-m, and had immunologic and clinical activity.

• Authors: W D Quan Jr, G E Dean, L Spears, C P Spears, S Groshen, J A Merritt, M S Mitchell
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 15 Issue 5 Pg. 2103-10 (May 1997) ISSN: 0732-183X [Print] United States
• PMID: 9164224 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Monoclonal
• Cancer Vaccines
• Acetylmuramyl-Alanyl-Isoglutamine
• N-acetylmuramyl-threonyl-isoglutamine

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (adverse effects, analogs & derivatives, immunology, therapeutic use)
• Adjuvants, Immunologic (adverse effects, therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, immunology, therapeutic use)
• Cancer Vaccines (adverse effects, immunology, therapeutic use)
• Drug Administration Schedule
• Female
• Humans
• Immunization Schedule
• Male
• Melanoma (immunology, secondary, therapy)
• Middle Aged