Efficacy of CAR-T-Cell-Based Immunotherapies in Patients With Glioma: A Systematic Review and Meta-Analysis.

Glioma is an aggressive intracranial malignancy associated with a poor prognosis and high mortality. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising immunotherapeutic approach for solid tumours; however, its application in glioma is constrained by several significant challenges. This study conducted a systematic review and meta-analysis to synthesise current methodologies and critically evaluate the clinical efficacy of CAR-T-cell-based immunotherapies in patients with glioma. A comprehensive literature search was performed across PubMed, Scopus, Web of Science and Embase using MeSH terms along with relevant keywords. The review process adhered to the PRISMA framework, applying clearly defined inclusion and exclusion criteria. Standard and augmented meta-analyses were employed to evaluate clinical outcomes, associated complications and potential publication bias. The study protocol was prospectively registered in PROSPERO under registration number CRD42022373297. Of 7723 retrieved records, 23 studies encompassing 306 patients with glioma met inclusion criteria. Efficacy analysis of 12 studies (n = 153 evaluable patients) demonstrated a pooled overall response rate of 16.9% (95% confidence interval [CI], 8.0%-32.2%), driven by complete responses in 8.1% (95% CI, 3.5%-17.8%) and partial responses in 13.1% (95% CI, 6.3%-25.5%) of patients. Stable disease was achieved in 46.6% (95% CI, 34.3%-59.3%); progressive disease was observed in 43.9% (95% CI, 27.7%-61.5%). Safety evaluation revealed grade ≥ 3 adverse events in 18.6% (95% CI, 10.0%-33.0%) of treated patients (n = 69 across 9 studies). Cytokine release syndrome affected 29.7% (95% CI, 9.3%-63.3%) (n = 80 across 9 studies), while immune effector cell-associated neurotoxicity syndrome developed in 12.9% (95% CI, 3.6%-37.0%) (n = 59 across 7 studies). This review demonstrated CAR-T-cell therapy to have promise in glioma, but evidence remains limited by heterogeneity and small samples. Larger standardised trials, systematic adverse-event reporting and mechanistic studies on constructs, dosing and combinations are needed. Biomarker discovery will refine patient selection, reduce risk and clarify the therapeutic role of CAR-T cells in glioma.