Ctim-26. Toxicity Profile of Car-T Cell Therapy in Glioblastoma: A Meta-Analysis of Cytokine Release Syndrome, Neurotoxicity, and Adverse Events

BACKGROUND Chimeric antigen receptor (CAR) T cell therapy is under investigation for glioblastoma (GBM), with early-phase trials reporting varied toxicity profiles. While CAR-T has demonstrated potential in hematologic malignancies, its safety in GBM remains incompletely characterized. This study meta-analyzes adverse event profiles, including cytokine release syndrome (CRS), neurological events, and overall toxicity in GBM. METHODS A systematic search was conducted through May 30, 2025, using PubMed, Cochrane Library, and conference proceedings from ASCO, SNO, ESMO, and AACR. Eligible studies were clinical trials of CAR-T therapy in GBM reporting CRS, neurological events, or any grade adverse events. Pooled incidence rates were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic, with values of 0–25% considered low, 26–50% moderate, and >50% high. Between-study variance was estimated using the Q-profile method with Hartung-Knapp adjustment. RESULTS Twelve phase I trials (N=147) were analyzed. The median age was 55 years (IQR: 42.8–60.5), and 35.3% of participants were female. Dose escalation strategies were reported in 46% of studies, while the remaining 54% used fixed or predefined dosing. Routes of CAR-T administration included intravenous (46%), intraventricular (23%), intracavitary (15%), and multiple or combined routes (15%). The median time from diagnosis to CAR-T infusion was 12.0 months (IQR: 11.05–15.0). The pooled incidence of CRS was 20.3% (95% CI: 3.7%–63.0%; I²=72.8%). Neurological events occurred in 41.0% of patients (95% CI: 22.4%–62.6%; I²=59.8%). The overall rate of any-grade adverse events was 59.5% (95% CI: 46.5%–71.2%; I²=35.0%). Median follow-up was 8.9 months (IQR: 6.3–22.8). CONCLUSIONS Adverse events are frequently observed in early-phase CAR-T trials for GBM, with considerable variability in CRS and neurotoxicity rates. These findings highlight the need for optimized dosing strategies, delivery routes, and toxicity mitigation approaches as CAR-T continues to advance in neuro-oncology.