Defining the effects of age and gender on immune response and outcomes to melanoma vaccination: a retrospective analysis of a single-institution clinical trials’ experience

Abstract

Background

The impacts of patient age and gender on immune response (IR) and clinical outcome after cancer vaccines are not known. We hypothesized younger and female patients would have higher IR rates and better survival.

Methods

Patients with resected stage IIB–IV melanoma in three clinical trials (Mel43, Mel44, Mel48) were vaccinated with 12 melanoma-associated peptides restricted by class I MHC. The cumulative incidence rate of CD8+ T cell responses (direct interferon-gamma ELIspot assay) by week 7 was compared by age and gender. Overall survival (OS) and disease-free survival (DFS) landmark analyses were compared by Kaplan–Meier estimates and in multivariate analyses.

Results

T cell responses were evaluated in 327 patients and detected in 50 % of males and 48 % of females, with no difference in IR by gender or menopausal status. Males had trends toward longer DFS (p = 0.12) and OS (p = 0.09). Cumulative incidence of IR was higher in patients <64 years of age versus older patients (p = 0.03). OS and DFS were similar by age group (p > 0.50). In multivariate modeling, younger age was associated with better IR (OR 0.40, p value 0.003), without an impact of age or gender on clinical outcomes.

Conclusion

These data support the hypothesis that older patients are less likely to develop T cell responses to a cancer vaccine. Nonetheless, significant proportions of older patients mount immune responses with comparable survival outcomes. Thus, these data support including older patients in cancer vaccine trials, but suggest value in stratifying patients by age </>64 years.

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Abbreviations

6MHP:

6 Melanoma helper peptides

12MP:

12 class I MHC-restricted peptides

DFS:

Disease-free survival

FDA:

Food and Drug Administration

IR:

Immune response

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Acknowledgments

This research was funded in part by the National Institutes of Health [NIH]/National Cancer Institute [NCI] grants NIH R01 CA057653 and CA 118386 and NIH R21 CA103528 awarded to Craig Slingluff, T32 CA163177 awarded to Yinin Hu/Craig Slingluff, and K25 CA181638 awarded to Nolan Wages, and Cancer Center Support Grant P30 CA044579.

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Correspondence to Adriana G. Ramirez.

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Conflict of interest

Craig Slingluff is an inventor of several peptides included in the vaccine that was administered during the clinical trials studied within this paper. The University of Virginia Licensing and Ventures Group holds the patents for those peptides, which have been licensed through the Ludwig Institute for Cancer Research to Glaxo Smith Kline. The remaining authors have nothing to disclose or competing interests in association with this study.

Additional information

Data included in this article were previously presented in two separate portions at the Society of Immunotherapy of Cancer 2014 Annual Meeting in Washington DC, USA, as a poster presentation, and the 2015 Academic Surgical Congress in Las Vegas, USA, as a plenary oral presentation.

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Ramirez, A.G., Wages, N.A., Hu, Y. et al. Defining the effects of age and gender on immune response and outcomes to melanoma vaccination: a retrospective analysis of a single-institution clinical trials’ experience. Cancer Immunol Immunother 64, 1531–1539 (2015). https://doi.org/10.1007/s00262-015-1758-5

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Keywords

  • Age
  • Gender
  • Peptide vaccines
  • Melanoma
  • Clinical trials
  • Outcomes