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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.

Authors :
Ramirez AG
Wages NA
Hu Y
Smolkin ME
Slingluff CL Jr
Source :
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2015 Dec; Vol. 64 (12), pp. 1531-9. Date of Electronic Publication: 2015 Sep 21.
Publication Year :
2015

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.<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
1432-0851
Volume :
64
Issue :
12
Database :
MEDLINE
Journal :
Cancer immunology, immunotherapy : CII
Publication Type :
Academic Journal
Accession number :
26392296
Full Text :
https://doi.org/10.1007/s00262-015-1758-5