A Multiphase Combined Treatment Including Individualized Multimodal Immunotherapy and Tumor Microenvironment Therapy for Glioblastoma: A Decade of Experience with Real-World Patients

Background/Objectives: A potential association between individualized multimodal immunotherapy (IMI) within a multiphase combined treatment strategy and prolonged survival was explored through retrospective real-world data analysis. Methods: The patient selection criteria were as follows: treatment after 27 May 2015, adults between ages 18 and 70, GB diagnosis and IDH1wt status documented, known MGMT promoter methylation status (methylated versus unmethylated), known status of OS, and no second malignancy. IMI is currently only accessible to patients with a >60 KPI and sufficient financial resources. Results: A total of 104 patients were identified, distributed as per MGMT methylation versus unmethylation status, respectively, as 18% female/25% male versus 23% f/38% m; the median age at intake was 54 y versus 50 y; the resection extent was 12 R0, 28 < R0 and three not documented versus 25, 28 and eight; and the median KPI at intake was 70 overall. Patients received a median of 37 versus 31 modulated electro-hyperthermia sessions, 37 versus 32 NDV injections, and two versus one dendritic cell vaccines. The median OS and percentage 2 y OS were 33.1 months and 69.7% versus 19.0 months and 35.4%. There were no major adverse reactions (ARs), but the AR burden increased with checkpoint inhibitor use. A 33-patient subset was analyzed on health-related quality of life (HRQoL) throughout IMI treatment, based on at least five EQ-5D-5L questionnaires available from intake. Mobility and self-care affected HRQoL less than usual activity, pain/discomfort and anxiety/depression. Throughout IMI, HRQoL remained stable. Before progressive disease, the median health utility index was 0.86, resulting in a median quality-adjusted life-months of 4.6 versus a median of 5.4 calendar months. Conclusions: Real-world observation indicates IMI may prolong GB patient OS while maintaining HRQoL.