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:
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
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MSK Authors
  1. Christian Grommes
    92 Grommes
  2. Alexandra Miller
    34 Miller
  3. Jacqueline Blair Stone
    24 Stone
  4. Dean Christian Carlow
    32 Carlow
  5. Lauren Rhea Schaff
    25 Schaff
  6. Ugur Sener
    14 Sener