Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial

Emily K. Ninmer, Hong Zhu, Kimberly A. Chianese-Bullock, Margaret Mehren, Naomi B. Haas, Merrick I. Ross, Lynn T. Dengel and Craig L. Slingluff ()
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Emily K. Ninmer: University of Virginia
Hong Zhu: University of Virginia
Kimberly A. Chianese-Bullock: University of Virginia
Margaret Mehren: Fox Chase Cancer Center
Naomi B. Haas: Fox Chase Cancer Center
Merrick I. Ross: MD Anderson Cancer Center
Lynn T. Dengel: University of Virginia
Craig L. Slingluff: University of Virginia

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract The critical roles of CD4+ T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes of a randomized multicenter phase II clinical trial (NCT00118274), where patients with high-risk melanoma received a multipeptide vaccine targeting CD8+ T cells (12MP) and were randomized to receive either of two vaccines for CD4+ (helper) T cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific helper peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary outcomes for T cell responses to 12MP, 6MHP, and tet were previously reported, suggesting immunogenicity of both vaccines but that CD8 T cell responses to 12MP were lower when tet was replaced with 6MHP. Here, in post-hoc analyses, we report durable prolongation of overall survival by adding 6MHP instead of tet. That benefit was experienced only by male patients. A favorable interaction of 6MHP and Cy is also suggested. Multivariable Cox regression analysis of the intent-to-treat population identify vaccine arm (12MP + 6MHP+Cy) and patient sex (male) as the two significant predictors of enhanced survival. These findings support the value of adding cognate T cell help to cancer vaccines and also suggest a need to assess the impact of patient sex on immune therapy outcomes.

Date: 2024
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DOI: 10.1038/s41467-024-46877-6

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