O6.03 * A PHASE II TRIAL OF AUTOLOGOUS DENDRITIC CELLS VACCINATION AND RADIO-CHEMOTHERAPY FOLLOWING FLUORESCENCE-GUIDED SURGERY IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS: PRELIMINARY CLINICAL RESULTS OF THE TRIAL

Abstract

BACKGROUND: Immunotherapy is emerging as a promising therapeutic modality for the treatment of glioblastoma (GBM). Recent clinical trials have supported the use of different therapeutic vaccines for high-grade gliomas, demonstrating promising feasibility and safety data. However, the wide variety of approaches and the limitations characterizing most studies preclude firm conclusions regarding efficacy. A phase II trial evaluating the efficacy and safety of autologous dendritic cells vaccination in addition to fluorescence-guided surgery and standard radio-chemotherapy with temozolomide in patients with newly diagnosed GBM was undertaken. PATIENTS AND METHODS: All consecutive patients aged 18 to 70 years who were candidates for resection of a suspected GBM were screened. An attempt at maximum resection was made in every case using fluorescence-guided surgery with 5-aminolevulinic acid. Less than 1 cc of residual tumour and histological confirmation of GBM were required for definite inclusion in the trial. Vaccines were prepared with autologous dendritic cells pulsed with tumour lysate and matured ex vivo. Vaccination calendar started before radiotherapy. Patients also received standard treatment consistent on radiotherapy with concomitant and up to 12 cycles of adjuvant temozolomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), safety, quality of life, and immune response. RESULTS: Thirty-two patients were screened between February 2009 and December 2011. One patient was excluded because of insufficient tumour resection (>1 cc of residual tumour). The mean age of the 31 included patients was 59 years. Median Karnofsky Performance Score (KPS) was 80% (range 60-100%). According to recursive partitioning analysis (RPA), 10% of the patients were RPA class III, 42% were class IV and 48% were class V. O6-methylguanine-DNA methyltransferase (MGMT) promoter was found to be unmethylated in 53% of the patients. Enough tumor lysate and dendritic cells were available in all cases to produce at least 6 vaccine doses. The median number of available vaccine doses was 11,2 (range, 6 to 17). Median PFS was 8.0 months and median OS was 27.4 months (95% CI: 20.9-33.0 months). No severe adverse events attributable to immunotherapy were identified. CONCLUSION: These results suggest that autologous dendritic cells vaccination is feasible and safe, and that the addition of this immunotherapy modality to gross total resection and standard radio-chemotherapy appears to increase survival in patients with newly diagnosed GBM.