Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial

SIMPLE SUMMARY: Among all intracranial tumors, 31.5% are malignant, and among those, glioblastomas account for 47%. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. Patients received monthly intradermal injections of allogenic dendritic cell vaccinations. The survival curves of the vaccinated populations were compared with patients from the GDC (Genomics Data Commons) database, which revealed that overall survival was 75% greater in the vaccinated glioblastoma group (16 to 28 months, hazard ratio 0.53) and 200% greater in the vaccinated astrocytoma grade 4 group (20 to 60 months, hazard ratio 0.18). Furthermore, seven patients remain alive to this day. We believe that the data reported here can foster the continued improvement of treatment protocols based on cellular immunotherapy. ABSTRACT: Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p < 0.001, hazard ratio 0.53, 95%CI 0.36–0.78, p < 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p < 0.05, hazard ratio 0.18, 95%CI 0.05–0.62, p < 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4–78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.