A Comprehensive Review of Immunotherapeutic Modalities in Glioblastoma: Mechanisms, Efficacy, and Safety Considerations †

BACKGROUND: Glioblastoma multiforme (GBM), the most aggressive primary brain malignancy in adults, is associated with poor prognosis and recurrence despite standard of care and newer immunotherapies. This warrants exploration of synergistic approaches such as combination immunotherapy for improved tumor control. METHODS: We initiated a systematic review of articles from 2015-2025 in PubMed, Embase, Scopus, Cochrane, and Web of Science if they assessed immunotherapy for GBM. RESULTS: We included 49 studies (n = 3002 patients) with no significant demographic differences across publications. Combination immunotherapy regimens demonstrated higher pooled ORRs in limited comparative analyses, though findings were driven by a small number of studies. Single-arm analysis for overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs), and ORR showed no significant differences among the groups. However, treatment-control arm analysis showed pooled ORs of 9.51 for combination immunotherapies and 0.44 in the control group. CONCLUSIONS: Combining immunotherapeutics across mechanisms may potentiate immune response effectiveness against GBM.