TAILIEUCHUNG - Routine use of low-dose glucarpidase following high-dose methotrexate in adult patients with CNS lymphoma: An open-label, multi-center phase I study

High-dose methotrexate (HD-MTX) has broad use in the treatment of central nervous system (CNS) malignancies but confers significant toxicity without inpatient hydration and monitoring. Glucarpidase is a bacterial recombinant enzyme dosed at 50units (u)/kg, resulting in rapid systemic MTX clearance. | Schaff et al. BMC Cancer 2022 22 60 https s12885-021-09164-x RESEARCH Open Access Routine use of low-dose glucarpidase following high-dose methotrexate in adult patients with CNS lymphoma an open-label multi-center phase I study Lauren R. Schaff1 Mina Lobbous2 Dean Carlow3 Ryan Schofield3 Igor T. Gavrilovic1 Alexandra M. Miller1 Jacqueline B. Stone1 Anna F. Piotrowski1 Ugur Sener1 Anna Skakodub1 Edward P. Acosta4 Kevin J. Ryan4 Ingo K. Mellinghoff1 Lisa M. DeAngelis1 Louis B. Nabors2 and Christian Grommes1 Abstract Background High-dose methotrexate HD-MTX has broad use in the treatment of central nervous system CNS malignancies but confers significant toxicity without inpatient hydration and monitoring. Glucarpidase is a bacterial recombinant enzyme dosed at 50 units u kg resulting in rapid systemic MTX clearance. The aim of this study was to demonstrate feasibility of low-dose glucarpidase to facilitate MTX clearance in patients with CNS lymphoma CNSL . Methods Eight CNSL patients received HD-MTX 3 or 6 g m2 and glucarpidase 2000 or 1000u 24 h later. Treatments repeated every 2 weeks up to 8 cycles. Results Fifty-five treatments were administered. Glucarpidase 2000u yielded gt 95 reduction in plasma MTX within 15 min following 33 34 doses and glucarpidase 1000u yielded gt 95 reduction following 15 20 doses 75 . Anti-glucarpidase antibodies developed in 4 patients and were associated with MTX rebound. In CSF glucarpidase was not detected and MTX levels remained cytotoxic after 1 nmol L n 8 and 6 h nmol L n 7 . Treatment was safe and well-tolerated. Radiographic responses in 6 of 8 patients 75 were as expected following MTX-based therapy. Conclusions This study demonstrates feasibility of planned-use low-dose glucarpidase for MTX clearance and sup- ports the hypothesis that glucarpidase does not impact MTX efficacy in the CNS. Clinical trial registration NCT03684980 Registration date 26 09 2018 . Keywords CNS lymphoma Methotrexate

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• BMC Cancer
• CNS lymphoma
• High dose methotrexate
• Central nervous system
• Bacterial recombinant enzyme
• Cancer patient pathways
• Colorectal cancer
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