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Leptomeningeal Metastases, a severe late stage form of cancer progression in which malignant cells metastasize to the subarachnoid space (SAS) and leptomeninges, has a mean survival rate of 3–6 months with treatment. Standard of care intrathecal chemotherapy, delivered via an Ommaya reservoir, is limited by poor diffusion within the SAS and acute drug-related neurotoxicity. Neurapheresis™ therapy (NA) is a novel therapy that uses a dual lumen intrathecal catheter and extracorporeal filtration system to filter cerebrospinal fluid (CSF) in a closed-loop. We have previously demonstrated the ability of NA to decrease cancer cell burden in artificial CSF in vitro. Here, NA is shown to enhance chemotherapeutic drug circulation, delivered intraventricularly, throughout the SAS in vitro. NA was tested with a cranial-spinal model of the SAS that included ventricular, cervical and lumbar sampling sites. Drug distribution was tested by comparing the circulation of a 6mg, 3mL ventricular bolus injection of Methotrexate (MTX) in PBS over 48 hours with and without NA (2.0 mL/min flow rate). Ventricular, cervical, and lumbar samples were collected at t=0.5, 4, 8, 12, 24, and 48 hours following drug administration and analyzed by a MTX-specific enzyme-linked immunosorbent assay (ELISA). Compared to controls, NA demonstrated increased, faster distribution of MTX throughout the neuraxis, with an average increase in MTX concentration of 63.7% and 171.5% in the cervical and lumbar sites, respectively, across time points from 4 to 24 hours. The NA system also rapidly decreased the high, potentially neurotoxic concentration of MTX in the ventricles immediately following drug administration and out to 12 hours post-injection. Future in vivo and in vitro testing focuses on pharmacokinetics (PK) in both animals and an advanced 3D-printed human cranial-spinal model to further evaluate the ability of the NA system to enhance MTX distribution throughout the SAS, while simultaneously removing circulating tumor cells.

EXTH-22. ENHANCED DRUG DELIVERY AND CIRCULATION WITH THE NEURAPHERESIS™ SYSTEM FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES