197 Chimeric antigen receptor T-cell therapy in glioblastoma: a systematic review and meta analysis of early phase clinical trials with GRADE assessment
Year: 2026
Type: conference-abstract
Abstract: Background Glioblastoma is the most common and most lethal primary malignant brain tumor in adults, with a median overall survival of 12 to 15 months despite maximal safe resection, radiotherapy, and temozolomide. Chimeric antigen receptor T-cell therapy has shown durable remissions in hematologic malignancies, but its activity in glioblastoma remains uncertain. No previous synthesis has formally pooled the available early-phase evidence using meta-analytic methods and certainty-of-evidence assessment.Methods This systematic review and meta-analysis was prospectively registered in PROSPERO (CRD420251237673) and conducted in accordance with PRISMA 2020. Scopus, PubMed, Web of Science, and CENTRAL were searched, with forward and backward citation tracking and trial registry screening. Eligible studies were phase I trials of chimeric antigen receptor T-cell therapy for glioblastoma. Proportions were pooled using generalized linear mixed models with logit transformation and Hartung-Knapp-Sidik-Jonkman-adjusted confidence intervals. Methodological quality was assessed with the Methodological Index for Non-Randomized Studies, and certainty of evidence with GRADE.Results Thirteen phase I trials including 178 patients, of whom 167 were evaluable, and seven target antigens met the eligibility criteria. The pooled best overall response rate across 10 studies (n = 126) was 3.6% (95% confidence interval, 0.0% to 35.0%), with moderate heterogeneity (I 2 = 40.9%; p = 0.085). Response was numerically higher with locoregional than intravenous administration (8% versus 0%), although this difference was not statistically significant. Cytokine release syndrome of any grade occurred in 19% of patients across 7 studies (n = 53). Treatment-related death was 1% (95% confidence interval, 0.0% to 5.0%) across 13 studies (n = 160), with one reported event. Neurotoxicity could not be pooled because reporting was highly inconsistent across 4 studies. Methodological quality scores ranged from 11 to 14 out of 16, and 5 of 13 studies met the prespecified threshold for low risk of bias. All pooled outcomes were rated very low certainty by GRADE.Conclusions Chimeric antigen receptor T-cell therapy for glioblastoma appears feasible and has a generally manageable safety profile with low treatment-related mortality, but objective antitumor activity remains limited and heterogeneous across targets, constructs, and delivery routes. Larger, standardized, and ideally comparative studies with harmonized toxicity reporting are needed before clinical benefit can be established.
Authors: Vincent Yuan, Ahmed Elhadi, Zaid Hasan, Naima Kebir
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225139610