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

Autor: Lauren R. Schaff, Mina Lobbous, Dean Carlow, Ryan Schofield, Igor T. Gavrilovic, Alexandra M. Miller, Jacqueline B. Stone, Anna F. Piotrowski, Ugur Sener, Anna Skakodub, Edward P. Acosta, Kevin J. Ryan, Ingo K. Mellinghoff, Lisa M. DeAngelis, Louis B. Nabors, Christian Grommes
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Cancer, Vol 22, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 1471-2407
DOI: 10.1186/s12885-021-09164-x
Popis: 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).
Databáze: Directory of Open Access Journals
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