IMCT-06SURVIVAL GAIN AND IMMUNE RESPONSE IN GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY BEFORE AND DURING ADJUVANT TEMOZOLOMIDE

Dendritic cell (DC) immunotherapy is gaining momentum in clinical cancer immunotherapy. We set-up a phase I-II study in patients with first diagnosis of glioblastoma (GBM) in which DC immunotherapy was associated to standard radiochemotherapy. The primary goal was to evaluate progression free survival (PFS) 12 months after surgery (PFS-12) as defined by RANO criteria. Safety, feasibility and evidence of immune response were also considered. Twenty-four patients were assessed. After gross-total resection (<10 ml residual volume at post-surgery MRI) patients underwent leukapheresis and radiochemotherapy followed by three biweekly intradermal injections of DC loaded with whole tumor lysate. Further DC injections were given on day 21 of the following cycles of adjuvant chemotherapy. Clinical, radiological and immunological follow-up were performed every two months. The treatment was well tolerated. Ten of 24 patients reached PFS-12. Median PFS was 10.2 months, median OS 19.4 months. These data compare favorably with those obtained using the EORTC nomogram for predicting survival in GBM patients and also with those of another parallel institutional study (FluoGlio) in which fluorescein-guided neurosurgery was followed by the standard treatment. Patients with PFS higher than the median had significantly higher numbers than other patients of active NK cells (i.e. producing interferon-gamma) and CD8+ T cells (producing interferon-gamma and expressing the effector/memory marker KLRG1) in peripheral blood but their number decreased after the first cycle of adjuvant temozolomide. The results encourage further investigation on DC immunotherapy and particularly on its interactions with concomitant chemotherapy.