CAR T-cell Therapy in Glioblastoma: A Systematic Review and Meta-analysis of Clinical Trials
Barbara Antonia Talah1, Pedro Bartkevitch Rodrigues2, Francisco Moraes3, Lucas Vital4, Mayara Marques5, Kristel Merida5
1Pontifical Catholic University of Parana, 2Miller School of Medicine, 3Federal University of Para, 4Federal University of Amazonas, 5NeuroDOC - Neurology, Neurosurgery, Spine Surgery, Neurology Exams, Neurological Rehabilitation and Pain Center
Objective:
To assess pooled survival, response and toxicity outcomes of CAR T-cell therapy in glioblastoma.
Background:
Glioblastoma is the most aggressive brain tumor. CAR T-cell therapy has emerged as an innovative approach targeting tumor-associated antigens such as EGFRvIII, IL13Rα2, HER2, and B7-H3, though clinical efficacy remains uncertain.
Design/Methods:
A systematic search of PubMed, Embase, and Cochrane identified clinical trials evaluating CAR T-cell therapy in GBM. Pooled median overall survival (OS) and progression-free survival (PFS) were estimated by the quantile estimation method. Analyses also included overall response rate (ORR), disease control rate (DCR), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), Grade 3–4 adverse events (AE), and death. Random-effects models estimated pooled proportions with 95% confidence intervals, and heterogeneity was assessed using I² and p-values from Cochran’s Q test. Analyses were performed in R (v4.5.1).
Results:
Fourteen trials comprising 190 patients receiving CAR T-cells therapy were included. The pooled median OS was 9.54 months (95% CI, 7.41-12.29), and median PFS was 2.25 months (95% CI, 1.29-3.93). The pooled ORR was 16% (95% CI, 8–31%; I² = 53.4%, p = 0.0182), while DCR reached 53% (95% CI, 43–63%; I² = 15.6%, p = 0.2956). Response stratification showed CR = 17% (95% CI, 2–73%; I² = 80.3%, p = 0.0063), PR = 14% (95% CI, 5–32%; I² = 62.0%, p = 0.0219), SD = 44% (95% CI, 36–52%; I² = 0.0%, p = 0.4493), and PD = 54% (95% CI, 41–66%; I² = 40.2%, p = 0.0731). Grade 3–4 AE occurred in 43% (95% CI, 29–58%; I² = 51.6%, p = 0.0237), and mortality was 78% (95% CI, 64–88%; I² = 47.4%, p = 0.0293).
Conclusions:
CAR T-cell therapy demonstrated modest tumor control, limited objective responses, and reduced survival. Despite DCR above 50%, high mortality and toxicity highlight the need for optimized CAR therapy.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.