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

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

Authors:	Schaff, L. R.; Lobbous, M.; Carlow, D.; Schofield, R.; Gavrilovic, I. T.; Miller, A. M.; Stone, J. B.; Piotrowski, A. F.; Sener, U.; Skakodub, A.; Acosta, E. P.; Ryan, K. J.; Mellinghoff, I. K.; DeAngelis, L. M.; Nabors, L. B.; Grommes, C.
Article 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
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 > 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. Conclusions: 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. Clinical trial registration: NCT03684980 (Registration date 26/09/2018). © 2022, The Author(s).
Keywords:	methotrexate; cns lymphoma; glucarpidase
Journal Title:	BMC Cancer
Volume:	22
ISSN:	1471-2407
Publisher:	Biomed Central Ltd
Date Published:	2022-01-01
Start Page:	60
Language:	English
DOI:	10.1186/s12885-021-09164-x
PROVIDER:	scopus
PMCID:	PMC8756618
PUBMED:	35027038
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123004882&doi=10.1186%2fs12885-021-09164-x&partnerID=40&md5=4dc664f84070d89d00c8e527edf74b54
Notes:	Article -- Export Date: 1 February 2022 -- Source: Scopus