Clinical outcomes after transition from weight-based to fixed-dose glucarpidase for high-dose methotrexate toxicity at a large academic medical center

Abstract

Introduction

Delayed methotrexate clearance can result in life-threatening toxicities including renal failure. Treatment includes vigorous hydration, urine alkalinization, leucovorin rescue, and glucarpidase. While traditional glucarpidase dosing is weight-based, its pharmacokinetic properties support possible use of non-weight-based dosing strategies. We evaluated clinical outcomes after transition from weight-based to fixed-dose glucarpidase for high-dose methotrexate (HDMTX) toxicity at a large academic medical center.

Methods

Adult patients requiring inpatient glucarpidase for HDMTX-associated renal insufficiency between October 2014 and June 2025 were retrospectively reviewed. Patients receiving weight-based glucarpidase prior to implementation of a fixed 2000-unit dosing strategy were included for comparison. The primary objective was to compare time to renal recovery. Secondary outcomes were exploratory and included time to glucarpidase administration, peak serum creatinine (Scr) fold-change, dialysis requirement, and hospital length of stay (LOS).

Results

Fourteen patients were included for analysis. Time to renal recovery was nearly identical between groups. The fixed-dose group received glucarpidase significantly sooner after HDMTX compared to the weight-based group (median 45.1 h vs. 71.5 h, p = 0.015) and had significantly lower max fold change in Scr (median 2.8-fold vs 3.8-fold, p = 0.034). The need for dialysis and median LOS trended towards fewer patients requiring dialysis (n = 0 vs n = 4, p = 0.070) and shorter LOS (19.1 days vs 39.3 days, p = 0.074) for the fixed-dose group.

Conclusions

Transitioning from a weight-based to 2000-unit fixed-dose for glucarpidase at our institution resulted in sustained efficacy and safety. Further research is necessary to define optimal glucarpidase dosing.