Adjuvant Vaccine Immunotherapy of Resected, Clinically Node-negative Melanoma: Long-Term Outcome and Impact of HLA Class I Antigen Expression on Overall Survival.

Publication Type:

Journal Article

Source:

Cancer immunology research (2014)

Keywords:

2014, Clinical Research Division, July 2014, Public Health Sciences Division

Abstract:

Associations between HLA class I antigen expression and efficacy of a melanoma vaccine (Melacine) were initially described in stage IV melanoma. Similar associations were observed in S9035, a phase III adjuvant trial evaluating Melacine for two years versus observation in patients with stage II melanoma. This report provides long-term results. The effects of treatment on relapse-free survival (RFS) and overall survival (OS) were evaluated, and pre-specified analyses investigated associations between treatment and HLA expression. Multivariable analyses were adjusted for tumor thickness, ulceration and site, method of nodal staging and sex. P=.01 was considered significant in subset analyses to account for multiple comparisons. For the entire study population of 689 patients, there were no significant differences in RFS or OS by arm. HLA serotyping was performed on 553 (80%) patients (vaccine 294, observation 259). Among the subpopulation with HLA A2 and/or HLA Cw3 serotype, vaccine arm patients (n=178) had marginally improved RFS (adjusted P=.02) and significantly improved OS compared with observation arm patients (n=145), with 10-year OS of 75% and 63%, respectively (hazard ratio 0.62, 99% CI 0.37-1.02, P=.01). There was no impact of HLA A2 and/or HLA Cw3 expression among observation arm patients. Analysis of mature data from S9035 indicates a significant OS benefit from adjuvant vaccine therapy for HLA A2 and/or HLA Cw3 expressing melanoma patients. The possibility of interactions between HLA type and outcome should be considered in future immunotherapy trials. Further investigations of melanoma-associated antigens present in Melacine and presented by HLA-A2 and HLA-Cw3 may be warranted.