EP12.09 EFFICACY AND SAFETY OF LOCOREGIONAL VS. INTRAVENOUS ADMINISTRATION OF CAR-T CELL THERAPY IN RECURRENT GLIOBLASTOMA: A SYSTEMATIC REVIEW AND SINGLE-ARM META-ANALYSIS

Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite standard treatment—including surgery, radiotherapy, and chemotherapy—recurrence is inevitable, and current options are limited. Chimeric antigen receptor T-cell (CAR-T) therapy has shown efficacy in hematologic malignancies and is being explored for GBM. The optimal route of administration has not been established, with locoregional routes (intraventricular, intracavitary, intratumoral) used to bypass the blood-brain barrier. This meta-analysis evaluates the efficacy and safety of locoregional CAR-T compared to intravenous delivery. MATERIAL AND METHODS A systematic review was conducted across six databases (PubMed, Embase, Scopus, Web of Science, CENTRAL, and Google Scholar). Primary outcomes included partial and complete response rates, progression-free survival, and overall survival. Secondary outcomes included disease progression and stable disease. A random-effects meta-analysis was performed using R software, and the ROBINS-I tool assessed risk of bias. RESULTS Fourteen studies with 148 patients were included. The partial response rate was 10.89% (95% CI: 4.73-23.12%), and the complete response rate was 6.85% (95% CI: 3.43-13.21%). Disease progression occurred in 52.46% (95% CI: 38.60-65.95%) of patients, and 28.22% (95% CI: 17.83-41.60%) had stable disease. Higher partial response rates were observed with locoregional routes (intraventricular/intracavitary). Thirteen studies reported median overall survival (2.5-11.8 months), with intravenous therapy showing better initial survival and locoregional routes offering prolonged benefits. Progression-free survival (1.3-5.2 months) was more consistent with intravenous routes. All studies were phase 1 trials with high risk of bias. CONCLUSION Locoregional CAR-T may offer a partial response advantage for recurrent GBM compared to intravenous delivery. While intravenous therapy showed better early survival, intracranial delivery provided prolonged benefits. However, the lack of statistical significance and high heterogeneity limit these findings. Larger, well-controlled studies are needed to confirm CAR-T’s potential in GBM.