ID #435 Individualized multimodal immunotherapy and tumor microenvironment therapy as part of a multiphase combined therapeutic strategy for adults with glioblastoma: a ten-year experience

Abstract

Improving overall survival for patients with Glioblastoma remains challenging. Treating a highly dynamic spatio-temporal heterogeneous infiltrating tumor process with fixed protocols using 1-2 alkylating agents for 6-12 months is not the solution. We developed a multiphase combined treatment strategy for glioblastoma patients, including individualized multimodal immunotherapy and tumor microenvironment therapy in each phase (PMID40075726; PMID38548421). For the current real world data analysis, 104 patients were selected out of the database with criteria: treatment after 27/05/2015, adults aged 18 to 70y, documented IDH1wt status, OS status known, absence of second malignancy and known MGMT-promoter methylation status (meth versus unmeth). Sex distribution was 18 female / 25 male in meth patients versus 23 /38 in unmeth patients. Median age at intake was 54y (26-70) versus 50y (18-68). Extent of resection was 12 R0, 28 < R0 and 3 not available versus 25, 28 and 8. Median KPI at intake was 70 (50-100) versus 70 (50-100), and was the only risk factor that significantly decreased over the observation period. Patients received in median 37 (0-138) versus 31 (4-147) sessions of modulated-electrohyperthermia, 37 (5-138) versus 32 (5-147) injections of Newcastle Disease Virus and 2 (0-4) versus 1 (0-6) DC vaccines. Median OS and percentage 2y OS were 30 months and 69.8% (95%CI: +11.9, -17.0) in meth patients versus 20 months and 37.4% (+13.2, -13.3) in unmeth patients. There were no major adverse reactions (AR), but the burden of AR was increasing when using checkpoint inhibitors. Data on quality of life in a subgroup of patients is reported separately. The beneficial effect of this treatment strategy on OS and quality of life in a larger group of real world patients confirms earlier data. It remains unclear how to draw evidence out of individualized medicine, although felt necessarily for patients with Glioblastoma.