Ctim-25. Chimeric Antigen Receptor T Cell Therapy for Glioblastoma: A Meta-Analysis of Efficacy From Early-Phase Clinical Trials

BACKGROUND Chimeric antigen receptor (CAR) T cell therapies represent a promising but still investigational approach for glioblastoma (GBM), a malignancy with limited effective treatment options. Despite interest, clinical outcomes remain variable. This meta-analysis evaluated median overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) across early-phase CAR-T trials in GBM. METHODS A systematic search was conducted through May 30, 2025, using PubMed, Cochrane, and conference proceedings. Eligible studies were CAR-T trials in GBM reporting median OS, PFS, or ORR. Pooled medians (OS, PFS) and logit-transformed proportions (ORR) were estimated using a random-effects model with continuity correction for zero-event studies. Heterogeneity was assessed using the I² statistic, with values of 0–25% considered low, 26–50% moderate, and greater than 50% high. Confidence intervals for between-study variance were estimated using the Q-profile method, and the Hartung-Knapp adjustment was applied for random-effects inference. RESULTS 13 phase I trials enrolling 160 patients were analyzed. Most studies (77%) included patients with recurrent/progressive GBM. The most frequent CAR targets were EGFRvIII (31%) and IL13Rα2 (23%), with other targets including HER2, GD2, B7-H3, EphA2, and dual EGFRvIII/IL13Rα2. The median age was 45.9 years (IQR: 45.9-61.75), and 36.1% of participants were female. Median follow-up was 8.9 months (IQR: 6.5-24), and the median time from diagnosis to CAR-T infusion was 12.0 months (IQR: 10.4-15.15). Prior radiotherapy was reported in 77% of studies. In the meta-analysis, the pooled median OS across was 7.6 months (95% CI: 5.27-9.94; I²=79.5%, p<0.0001). The pooled median PFS was 2.51 months (95% CI: 0.99-4.03; I²=75.8%, p=0.0081). The pooled ORR was 12.2% (95% CI: 5.3%-25.5%; I²=46.2%). CONCLUSIONS CAR-T therapy in GBM shows early signs of clinical activity but remains limited in efficacy. Next generation efforts to refine constructs, optimize timing, and improve patient selection in future trials are ongoing.