Adverse Effects in Tumor Vaccines for High Grade Primary Brain Tumors: A Comparative Meta-analysis

Introduction: Peptide, dendritic cell, and natural killer (NK) cell vaccines are potent immunotherapeutic agents for tumor targeting. However, the safety profile of these agents, particularly concerning autoimmune events, is not well established.

Methods: A comprehensive literature search was conducted across PubMed, Google Scholar, Cochrane, and Scopus databases, adhering to PRISMA guidelines, with random-effects meta-analysis assessing serious adverse outcomes. All reported results are pooled estimates.

Results: From 1004 screened studies, 4 comparative clinical trials and 25 single-cohort studies, encompassing 915 patients, were included. Studies included peptide vaccines (10 studies, 174/915 patients), dendritic cell vaccines (17 studies, 718/915 patients), and NK cell vaccines (2 studies, 23/915 patients). The mean age was 43.9 years (95%CI:[36.36-51.46]), and 42.4% were female (238/563, 95%CI:[36.82-48.06]). Intradermal or intramuscular administration was most common (708/915, 66.99%, 95%CI:[50.35-83.63]). Most patients had glioblastoma (833/915, 84.3%, 95%CI:[76.16-92.45]), or other gliomas (70/915, 14.75%, 95%CI:[6.62-22.88]). Compared to standard of care, there was no significant difference in the incidence of serious toxicity (2/511, OR: 5.00, 95%CI:[0.22-112.34]) or grade 3 and higher adverse events (OR: 0.89, 95%CI:[0.36-2.19]). Across all 29 studies, common side effects included local skin reactions (19.15%, 95%CI:[8.1-30.2]) and fever (1.34%, 95%CI:[0.45-2.23]). Rare events included lymphopenia (6/915, 1.22%, 95%CI:[0.36-2.08]), cerebral edema (5/915, 1.33%, 95%CI:[0.6-2.06]), and autoimmune hepatitis (5/915, 1.19%, 95%CI:[0.34-2.04]).

Conclusion : This is the first comprehensive comparative meta-analysis to highlight a favorable safety profile for tumor vaccines in the treatment of high grade primary brain tumors.