ATIM-13. ALLOGENEIC TUMOR LYSATE/AUTOLOGOUS DENDRITIC CELL VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA: RESULTS OF CLINICAL TRIAL MC1272

Abstract

INTRODUCTION: Dendritic cell (DC) vaccines for glioblastoma multiforme (GBM) have been promising in pre-clinical studies but widespread clinical translation has been hampered by issues related to immune editing for vaccines targeting specific antigens and feasibility / scalability for tumor lysate-based vaccines. We report findings from a clinical trial combining a DC vaccine strategy that addresses these issues with standard therapy in newly diagnosed GBM. METHOD(S): Twenty adult patients with resected newly diagnosed GBM who had completed radiation/concurrent temozolomide were enrolled. DC's were generated in vitro from patients' CD14+ monocytes with an optimized technique for DC maturation. Vaccines were generated by pulsing autologous DC's with allogeneic tumor lysate from two allogeneic patient-derived human GBM cell cultures with defined tumor antigen expression. Patients received temozolomide plus vaccine for up to 6 cycles followed by vaccine alone for up to 6 cycles. RESULT(S): Patients enrolled were relatively enriched for poor prognostic factors (45% subtotal resection, 25% multifocal, 20% bilateral, 95% IDH wild type, 70% MGMT promotor unmethylated). Vaccine manufacture was successful (>= 15 doses of mature, > 70% CD83+ DC's) in all patients. Treatment has been well tolerated with only grade 1 - 2 toxicities (fever, rash, fatigue) potentially related to the vaccine. Increased circulating tumorassociated antigen-specific CD8 T-cells have been demonstrated post-vaccination with dextramer flow cytometry. Median OS was 20.5 months and PFS was 9.7 months. 30% of patients remain progression-free at nearly 3 years. CONCLUSION(S): Autologous mature DC/allogeneic tumor lysate vaccines in combination with temozolomide are safe, feasible, and generates tumor antigen-specific immune responses in newly diagnosed GBM patients. Median OS and PFS are relatively prolonged compared to historical controls, particularly in light of poor baseline prognostic factors. More intriguing is a prolonged tail of progression-free survival in almost one third of patients.