Efficacy and Safety of Actively Personalized Neoantigen Vaccination in the Management of Newly Diagnosed Glioblastoma: A Systematic Review

PURPOSE: Glioblastoma (GBM) shows frequent relapse and is highly resistant to treatment; therefore, it is considered fatal. Various vaccination protocols that have been tested in patients with GBM, which is the most common and aggressive primary brain tumor, have indicated safety and efficacy, to some extent, when used alone or in combination with standard of care. Recently, neoantigen-based personalized vaccines have shown tremendous immunogenicity and safety in GBM. We aimed to systematically review the medical literature for clinical trials to evaluate the efficacy and safety of neoantigen-based personalized vaccines for newly diagnosed GBM. METHODS: We conducted a literature search for clinical trials on PubMed, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov until March 20, 2021. The primary outcomes of interest were immunogenicity and safety of the therapy. Efficacy outcomes, such as progression-free survival and overall survival, were secondary outcomes of interest. RESULTS: Two clinical trials involving 24 patients were included in this review. High immunogenicity was observed in both studies. The GAPVAC-101 trial reported 50% APVAC1-induced and 84.7% APVAC2-induced immunogenicity with CD8+ and CD4+ T cell responses in 92% (12/13) and 80% (8/10) immune responders, respectively. Two out of five patients showed CD4+ and CD8+ T cell responses in the study by Keskin et al. Dexamethasone use had limited immunogenicity in a trial by Keskin et al (6/8). No serious treatment-related adverse events were reported. CONCLUSION: Actively personalized vaccines aimed at unmutated peptides and neoantigens for patients with GBM are safe and highly immunogenic, particularly when administered in combination. Larger studies are warranted to investigate the role.