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 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), 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. Median follow-up was 5.6 years. No significant differences in RFS or OS were found by GM-CSF status. Participants vaccinated at two sites compared to one had significantly improved RFS (HR 0.59, 95%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.