Long-term Outcomes of Helper Peptide Vaccination for Metastatic Melanoma

Objective: The objective of this study was to compare the long-term outcome of patients with metastatic melanoma vaccinated with 6MHP to that of a group of unvaccinated historical controls. Background: A multipeptide vaccine (6MHP), designed to induce helper T cells against melanocytic and cancer-testis antigens, has been shown to induce specific Th1-dominant CD4+ T cell responses. Methods: The 6MHP vaccine was administered to patients with metastatic melanoma. Circulating CD4+ T cell responseswere measured by proliferation or direct IFN-gamma ELIspot assay. Overall survival of vaccinated patients was compared to a group of clinically comparable historical controls using multivariable Cox regression analysis and Kaplan-Meier survival analysis, taking into account age, metastatic site, and resection status. Results: Across 40 vaccinated patients and 87 controls, resection status (HR 0.54, P = 0.004) and vaccination (HR 0.24, P < 0.001) were associated with improved overall survival. Forty pairs of vaccinated patients and controls were matched by metastatic site, resection status, and age within 10 years. Median survival was significantly longer for vaccinated patients (5.4 vs 1.3 years, P < 0.001). Among the vaccinated patients, the development of a specific immune response after vaccination was associated with improved survival (HR 0.35, P = 0.040). Conclusions: Helper peptide vaccination is associated with improved overall survival among patients with metastatic melanoma. These data support a randomized prospective trial of the 6MHP vaccine.