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.

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).

参与者被随机分配到四个治疗组之一：单部位12MP（A组），单部位12MP + GM-CSF（B组），双部位12MP（C组），以及双部位12MP + GM-CSF（D组）。

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).

该试验旨在通过GM-CSF状态定义的疫苗组（B + D组对比A + C组）和疫苗接种部位（A + B组对比C + D组）来检测免疫原性差异。

For this analysis, overall survival(OS) and recurrence-free survival (RFS) were evaluated by these vaccine groups.

在本分析中，通过这些疫苗组评估了总生存（OS）和无复发生存（RFS）。

Results

All eligible participants (n = 121) were evaluated.

所有符合条件的参与者（n = 121）均进行了评估。

The median follow-up was 5.6 years.

中位随访时间为5.6年。

No significant differences in RFS or OS were observed by GM-CSF status.

根据GM-CSF状态，未观察到RFS或OS有显著差异。

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).

与单点接种相比，双点接种的参与者RFS显著改善[风险比(HR), 0.59; 95% 置信区间(CI), 0.38-0.93; P = 0.02]，并且OS有改善趋势(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.

在里程碑式的多变量分析中，双部位接种是在调整了CD8+ T细胞反应和其他预后因素后，唯一显著预测无复发生存期（RFS）的变量（HR，0.55；95% CI，0.34-0.88；P = 0.01）。

Conclusions

These results challenge the use of GM-CSF as a local vaccine adjuvant and support two-site vaccination.

这些结果质疑了GM-CSF作为局部疫苗佐剂的使用，并支持双部位接种。

Future work to characterize the locoregional immune response to cancer vaccination at the injection site and vaccine-draining lymph nodes is warranted.

有必要进行未来的工作，以表征癌症疫苗接种部位和疫苗引流淋巴结的局部区域免疫反应。