Persistent immunity and survival after immunization with a HER2/neu (HER2) vaccine.

3010 Background: Our initial vaccine studies showed that optimally treated breast cancer patients can be immunized against HER2 during active immunization. The majority of patients developed T-cell immunity to HER2 peptides and protein and also epitope spreading (ES). The goal of this study was to determine if patients previously immunized with a HER2 vaccine had persistent immunity years after active immunization and to assess their clinical outcome in terms of overall survival (OS). METHODS Subjects eligible for this IRB-approved long term follow-up (LTFU) study: (1) had HER2+ breast cancer and were immunized between 1996-1999 in a phase I HER2 peptide vaccine trial, (2) were at least 1 year out from their last vaccine, and (3) if donating blood samples could not be receiving chemotherapy. 52 patients (37 stage IV, 15 stage III) were identified and 21/52 patients (12 stage IV, 9 stage III) were determined to be living. All 21 subjects were contacted by letter and sent a LTFU Questionnaire. OS was defined as the time between date of vaccine study entry and death or last follow-up and was estimated using the Kaplan-Meier method. Cox proportional hazards were used to determine associations between OS and known clinical and vaccine-related immunologic factors; analyses included all 52 subjects. Long-term T-cell immunity was evaluated using IFN-γ ELISPOT assay. RESULTS Median follow-up time for the 21 patients still alive was 112 months (range, 104-126 months). Blood samples were collected in 10/21 subjects and 6/8 (75%) evaluble patients had persistent T-cell immunity to immunizing HER2 peptides; and 7/8 patients (88%) had T-cell immunity specific for HER2 protein and peptides not contained in their immunizing mix (defined as ES). In multivariate analysis, number of chemotherapy regimens prior to vaccination (HR=5.7 (CI 95%, 1.5-23; p=<0.001)), and development of ES after HER2 vaccination (HR=0.34 (CI 95%, 0.12-1.0; p=0.05)) were independent predictors of OS. Median OS for 33 subjects who developed ES was 84 months vs 25 months for 16 subjects who did not develop ES. CONCLUSIONS HER2-specific T-cell immunity elicited with active immunization is durable years after vaccination has ended and the generation of ES is an independent predictor of OS. No significant financial relationships to disclose.