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- Title
Routine use of low-dose glucarpidase following high-dose methotrexate in adult patients with CNS lymphoma: an open-label, multi-center phase I study.
- Authors
Schaff, Lauren R.; Lobbous, Mina; Carlow, Dean; Schofield, Ryan; Gavrilovic, Igor T.; Miller, Alexandra M.; Stone, Jacqueline B.; Piotrowski, Anna F.; Sener, Ugur; Skakodub, Anna; Acosta, Edward P.; Ryan, Kevin J.; Mellinghoff, Ingo K.; DeAngelis, Lisa M.; Nabors, Louis B.; Grommes, Christian
- Abstract
<bold>Background: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>Fifty-five treatments were administered. Glucarpidase 2000u yielded > 95% reduction in plasma MTX within 15 min following 33/34 doses (97.1%) and glucarpidase 1000u yielded > 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 (3299.5 nmol/L, n = 8) and 6 h (1254.7 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.<bold>Conclusions: </bold>This study demonstrates feasibility of planned-use low-dose glucarpidase for MTX clearance and supports the hypothesis that glucarpidase does not impact MTX efficacy in the CNS.<bold>Clinical Trial Registration: </bold>NCT03684980 (Registration date 26/09/2018).
- Subjects
METHOTREXATE; BACTERIAL enzymes; LYMPHOMAS; CENTRAL nervous system; ADULTS
- Publication
BMC Cancer, 2022, Vol 22, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-021-09164-x