ATIM-28. IMMUNE PROFILES AT START OF TEMOZOLOMID-BASED STANDARD TREATMENT AND DC-BASED IMMUNOTHERAPY STRONGLY CORRELATE WITH OVERALL SURVIVAL OUTCOME IN GBM PATIENTS

Abstract

DC-vaccination integrated in multimodal temozolomid-based treatment for patients with GBM prolong OS in a fraction of patients. Biomarkers predicting outcome after active specific immunotherapy, however, fail. Blood samples from 134 adults, randomized for DC-vaccination during or after TMZ maintenance (TMZm), were taken before and after radiochemotherapy. Data from circulating lymphocytes were determined by FACS in 101 patients. To quantify immune profiles more systematically, nonlinear features of these data were introduced, corresponding to all meaningful ratios between immune cell subpopulations. To quantify immune profile changes during radiochemotherapy for each such quantity, the ratio of its values after/before radiochemotherapy was also calculated. Canonical correlation analysis was performed exhaustively between all possible combinations of these quantities taken 1, 2 or 3 at a time versus OS. Median OS of the total group of patients was 18 months, 2-year OS was 31.3% (+4). There was no difference in OS for patients treated with immunotherapy during versus after TMZm. Patients with postoperative residual tumor volume had a significantly worse median OS (16 versus 20 months). For the entire population, no strong correlations were detected between the immune profiles and OS. However, stratifying the patients into subgroups defined by extent of resection (residual tumor volume RTV = 0 or >0) and vaccination schedule (during or after TMZm), and repeating this analysis for each of the 4 subgroups, revealed for all subgroups strong correlations between FACS data immune profiles derived from the pre- and post-radiochemotherapy blood samples and ultimate OS of the patients. These data suggest strong influences from the immune status at start of treatment on the OS outcome of the patients. The data depict the first in silico oncology model using immune profiles to potentially predict outcome of clinical risk profile-stratified patients treated with standard treatment and immunotherapy (www.chic-vph.eu).