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

## TL;DR

This paper reviews immunotherapy options for glioblastoma, focusing on their effectiveness, safety, and potential for improving patient outcomes.

## Contribution

The study systematically evaluates combination immunotherapies for glioblastoma and suggests they may enhance immune response effectiveness.

## Key findings

- Combination immunotherapy regimens showed higher pooled overall response rates compared to controls.
- No significant differences in survival or adverse events were observed among treatment groups.
- Combining immunotherapeutics across mechanisms may improve tumor control in glioblastoma.

## Abstract

Glioblastoma multiforme (GBM) is an aggressive brain cancer that is resistant and often recurrent when treated with traditional therapies. This systematic review and meta-analysis explores new immunotherapy options for GBM, specifically focusing on their abilities to provide adequate tumor control, improve survival outcomes, and limit off-target toxicities. We reviewed various types of immunotherapeutic regimens to provide insight into how these treatments could improve patient outcomes and help overcome the challenges of current interventions. This work could guide future research and clinical approaches in treating GBM, ultimately contributing to more effective treatment regimens for patients.

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.