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

Author

Listed:
  • Emily K. Ninmer

    (University of Virginia)

  • Hong Zhu

    (University of Virginia
    Cancer Center)

  • Kimberly A. Chianese-Bullock

    (University of Virginia
    Cancer Center)

  • Margaret Mehren

    (Fox Chase Cancer Center)

  • Naomi B. Haas

    (Fox Chase Cancer Center
    University of Pennsylvania)

  • Merrick I. Ross

    (MD Anderson Cancer Center)

  • Lynn T. Dengel

    (University of Virginia)

  • Craig L. Slingluff

    (University of Virginia
    Cancer Center)

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.

Suggested Citation

  • Emily K. Ninmer & Hong Zhu & Kimberly A. Chianese-Bullock & Margaret Mehren & Naomi B. Haas & Merrick I. Ross & Lynn T. Dengel & Craig L. Slingluff, 2024. "Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46877-6
    DOI: 10.1038/s41467-024-46877-6
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    References listed on IDEAS

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    1. Leon, Andrew C. & Heo, Moonseong, 2009. "Sample sizes required to detect interactions between two binary fixed-effects in a mixed-effects linear regression model," Computational Statistics & Data Analysis, Elsevier, vol. 53(3), pages 603-608, January.
    2. Ugur Sahin & Petra Oehm & Evelyna Derhovanessian & Robert A. Jabulowsky & Mathias Vormehr & Maike Gold & Daniel Maurus & Doreen Schwarck-Kokarakis & Andreas N. Kuhn & Tana Omokoko & Lena M. Kranz & Mu, 2020. "An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma," Nature, Nature, vol. 585(7823), pages 107-112, September.
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