Adriana G Ramirez1, Nolan A Wages2, Yinin Hu3, Mark E Smolkin2, Craig L Slingluff4. 1. Department of Surgery, University of Virginia, PO Box 800709, Charlottesville, VA, 22908, USA. agr5e@virginia.edu. 2. Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA. 3. Department of Surgery, University of Virginia, PO Box 800709, Charlottesville, VA, 22908, USA. 4. Department of Surgery, University of Virginia, PO Box 800709, Charlottesville, VA, 22908, USA. CLS8H@hscmail.mcc.virginia.edu.
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.
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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