CTIM-20. MR-MEASURED ADC AND FLUID FLOW AS PREDICTORS OF DECREASED PROGRESSION-FREE SURVIVAL IN PRIMARY BRAIN TUMOR PATIENTS RECEIVING IL12RA2 CAR-T THERAPY

Abstract BACKGROUND IL13Rα2-targeted CAR-T cells are a promising therapy for aggressive primary brain tumors, but it remains unknown why survival benefit between patients is heterogenous. MR imaging of targeted tumors reveals changes in tumor physiology, but it remains unclear whether these changes are progression related or immune-modulated. To investigate, we performed image analysis on perfusion and diffusion MRI. METHODS A Phase 1 study of IL13Rα2-targeted CAR-T cells was performed at City of Hope National Medical center. Patients were imaged using diffusion-weighted MRI, and with DCE-MRI at two timepoints: 1) post-resection and prior to CAR-infusion, and 2) after receiving 3 infusions of CARs. The patient cohort consisted of 39 patients, suffering from primary recurrent GBM, astrocytoma, oligodendroma, or ependymoma, with 16 female and 28 male individuals. The apparent diffusion coefficient of water (ADC) was measured with diffusion-weighted MRI, and the interstitial fluid flow velocity (IFF) was measured using DCE-MRI. RESULTS Increasing tumor density, and decreasing tumor IFF heterogeneity were associated with decreased progression-free survival. Patients with less-dense tumors after 3 CAR-T infusions had increased median progression-free survival of 5 months (25th percentile ADC > 535 E-6 mm2/sec, log-rank p < 1E-4), and patients with higher IFF heterogeneity had increased progression-free survival of 6 months (std(IFF) > 0.06 mm2/s, log-rank p <1E-4). IFF and ADC 25th percentile after CAR-T therapy were not significantly correlated (Pearson r = 0.30, p > 0.05). CONCLUSIONS CAR-T therapy success may be determined as early as 1 month after beginning CAR-T therapy in patients with aggressive primary brain tumors. Standard medical imaging, such as diffusion-weighted and DCE-MRI may provide evidence that therapy is successful. Conversely, these same biomarkers can be an early warning that treatment is ineffective, and may allow for better decision making for future participation in the trial, or if modifications need to be made to better administer CAR-T cells to these patients.