Leptomeningeal disease (LD) from IL13Rα2-positive brain cancer is associated with poor prognosis, with current therapies offering limited efficacy and control. IL13Rα2-targeted CAR-T cells represent a promising therapeutic strategy, potentially overcoming the barriers of the central nervous system. All participants in this phase 1 study (NCT04661384) had IL13Rα2+ CNS tumors with leptomeningeal dissemination and received four serial intrathecal infusions of IL13Rα2-directed CAR T cells. One participant received a reduced dose (10M, 50M, 50M, 50M) due to due to low Tn/mem yield from the apheresis, and thus was not included for response assessment. Arm 1 (glioblastoma, n=4) had a median survival of 8.7 months, with one subject achieving stable disease. Arm 2 (ependymoma/ medulloblastoma, n=4) had a median survival of 6.5 months with two subjects still surviving after after 18 months, and two subjects achieving stable disease. Dynamic contrast-enhanced MRI was used to monitor tumor perfusion and vascularity, with all patients receiving imaging ~1 month after beginning treatment. In non-survivors, venous blood return rate (kep) was positively associated with survival time (Pearson r = 0.85, p<0.05, n=6), and tumor blood volume fraction (vp)) was negatively associated with survival (Pearson r = -0.94, p < 0.01, n=6).Imaging demonstrates surviving patients in Arm 2 had lower blood volume in tracked brain metastases (vp,surviving = 0.26+/-0.04 n = 2, vp,non-surviving = 0.44+/-0.09 n=2, mean +/- std) than non-survivors in Arm 2. Initial results from this Phase I trial show promise for patients with metastatic ependymoma. Treatments were well-tolerated with expected SAEs. DCE-MRI analysis may prove as a useful tool for prognosis for patients with LD while receiving IL13Rα2-targted CARs, indicating that blood plasma fraction and venous return rate of leptomeningeal lesions may be biomarkers of extended survival.
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