HGG-05. CAN MULTIMODAL IMMUNOTHERAPY REPLACE RADIOCHEMOTHERAPY IN COMPLETELY RESECTED ADULT GBM?

Adults with GBM always relapse, even after complete resection. Therefore radiotherapy with broad margins around the resection cavity is mandatory part of the initial standard of care for these patients, aimed to maximize the local tumor control. Chemotherapy is aimed as function as radiosensitizer and to prolong disease-free survival. Nevertheless, most patients show local and/or even distant tumor re-occurrence more or less shortly after multimodal primary treatment. Hypotheses for this are the infiltrative character of the tumor cells, the residing non-dividing glioma cancer stem cells, chemoresistance, etc. IOZK was confronted with a patient (EORTC RPA class IV) who refused radiochemotherapy and maintenance chemotherapy after complete resection of a left occipital glioblastoma. Pathology showed tissue necrosis, angiogenesis, mitosis and atypical tumor cell nuclei. Molecular classification revealed glioblastoma, IDH wildtye, subtye RTK I. After immunodiagnostic blood sampling, the patient was treated with multimodal immunotherapy consisting of 2 cycles of 6 days Newcastle Disease Virus (NDV) infusions and local modulated electrohyperthermia (mEHT) sessions plus an autologous DC vaccine loaded with serum-derived NDV/mEHT-induced antigenic microparticles + NDV, and additionally four more treatments with NDV infusions + mEHT. Treatment was conducted without any side effect. We observed the induction of tumor antigen-specific IFN-producing T cells measured upon ex vivo stimulation with autologous DCs loaded with a GBM cell line in ELISPOT. At time of writing, 15 months after resection, the patient remains in complete remission with optimal Karnofsky performance index and good quality of life. The % PFS at 12 months in the Stupp 2005 paper is for the total group of patients with radiotherapy alone 9.1% (95%CI 5.8–12.4m). The patient history points to a potential change in paradigm that microscopic infiltrating GBM tumor cells might be brought under permanent control through the combined action of NDV, mEHT and the induction of memory T cells.