Impact of GM-CSF and Two-Site Vaccination on Clinical Outcomes after Multipeptide Vaccination for Melanoma: Long-term Analysis of a Randomized Phase II Trial.

PURPOSE: We report the long-term clinical outcomes of a multicenter, randomized phase II trial (NCT00089193) that tested immunogenicity of a vaccine composed of 12 class I MHC-restricted melanoma peptides (12MP), with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant and administered at one or two sites in patients with resected high-risk melanoma.

PATIENTS AND

METHODS

Participants were randomized to one of four treatment arms: 12MP at one site (arm A), 12MP + GM-CSF at one site (arm B), 12MP at two sites (arm C), and 12MP + GM-CSF at two sites (arm D). The trial was powered to detect differences in immunogenicity by vaccine groups defined by GM-CSF status (arms B + D vs. A + C) and vaccine sites (arms A + B vs. C + D). For this analysis, overall survival (OS) and recurrence-free survival (RFS) were evaluated by these vaccine groups.

RESULTS

All eligible participants (n = 121) were evaluated. The median follow-up was 5.6 years. No significant differences in RFS or OS were observed by GM-CSF status. Participants vaccinated at two sites compared with one had significantly improved RFS [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.38-0.93; P = 0.02] and a trend to improved OS (HR, 0.64; 95% CI, 0.39-1.06; P = 0.08). On landmark multivariable analysis, two-site vaccination was the only significant predictor of RFS (HR, 0.55; 95% CI, 0.34-0.88; P = 0.01) after adjusting for CD8+ T-cell response and other prognostic factors.

CONCLUSIONS

These results challenge the use of GM-CSF as a local vaccine adjuvant and support two-site vaccination. Future work to characterize the locoregional immune response to cancer vaccination at the injection site and vaccine-draining lymph nodes is warranted.