Multiplex bead-based measurement of humoral immune responses against tumor-associated antigens in stage II melanoma patients of the EORTC18961 trial

Abstract

Purpose: Determine the prognostic and predictive significance of tumor associated antigen (TAA)-specific serum antibodies in melanoma patients of a large adjuvant vaccination phase III trial. Patients and methods: Serum IgG antibodies were measured against a panel of 43 antigens by a bead-based multiplex assay in 970 stage II melanoma patients of the EORTC18961 trial, evaluating adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation. Primary end point was relapse-free survival (RFS). Patients' sera at baseline, after 12 and 48 weeks of study treatment and at the last available time point (at recurrence/remission) were evaluated. Results: Prognostic clinical variables are gender, surgical confirmation of lymph node-negative status, Breslow thickness and ulceration of the primary. Prognostic spontaneous antibody responses were associated with a significant dismal (GM2, Rhod_E2, SSX2) or good prognosis (CyclinB1, SCYE1v1) for RFS, distant metastasis-free (DMFS) or overall survival (OS). Predictive spontaneous antibody responses based on significant interaction with treatment were RhodN p = 0.02, Rab38 p = 0.04 for RFS, RhodE2 p = 0.006, Recoverin p = 0.04 for DMFS and RhodE2 p = 0.003; Recoverin p = 0.04, NA17.A p = 0.04, for OS respectively. The subgroups of patients according to antibody responses for RFS were determined for RhodN sero-negative (n = 849, HR = 1.07, p = 0.6); RhodN sero-positive (n = 121,HR = 0.42, p = 0.01) and Rab38 sero-negative (n = 682, HR = 1.12, p = 0.42), Rab38 sero-positive (n = 288, HR = 0.65, p = 0.04) patients respectively. Conclusion: We identified prognostic serum antibody responses against TAA in stage II melanoma patients. A set of antibody responses correlated with a beneficial outcome for GM2 vaccination.