Immunotherapy of melanoma.

Melanoma is one of the first tumors for which several types of immunotherapy have been applied extensively. It is becoming clear that although only a minority of patients respond to immunotherapy, those who do have a major clinical response experience an improvement in survival. Melanoma vaccines (active specific immunotherapy) have elicited clinical remissions in advanced disease, in some instances for years. They may have extended survival in resected stage II or III disease, although the results of controlled, randomized trials in these stages are still pending. Perhaps their major advantage is their nearly total lack of significant systemic toxicity. Gene-modified whole-cell vaccines, newer constructs involving cell membranes on synthetic beads, and purified immunogenic peptides are interesting second-generation vaccines. Cytokines such as interferon-alpha and interleukin-2 also have had a beneficial effect in approximately 20% of patients with advanced disease, with a suggestion of higher rates of response when interferon is combined with a vaccine. A randomized, controlled Intergroup study has shown that interferon-alpha at 10 million U/m2/d three times weekly for 2 y is superior to observation alone in prolonging relapse-free and overall survival in resected stage III patients. Other such trials are necessary to prove the usefulness of immunotherapy in melanoma, but its promise as a new approach to a difficult disease is already evident.