Low-Dose Planned Glucarpidase Allows Safe Outpatient High-Dose Methotrexate Treatment for CNS Lymphoma

High-dose methotrexate (HD-MTX) is the backbone of curative therapy for CNS lymphoma. Because of toxicity, MTX is administered in the inpatient setting along with hyperhydration and monitoring until MTX clearance is documented (3-5 days). Frequent hospitalizations result in patient time away from work, home, and exposure to potential iatrogenic/nosocomial complications. Here, we aim to demonstrate feasibility of HD-MTX administration in the outpatient setting with low-dose glucarpidase facilitating clearance.

This is a prospective nonrandomized study of outpatient HD-MTX followed by glucarpidase 2000u (ClinicalTrials.gov identifier: NCT03684980). Eligible patients had CNS lymphoma, creatinine <1.3 mg/dL, and previously tolerated HD-MTX. Patients were enrolled between May 2020 December 2021 for one HD-MTX treatment. Patients could re-enroll for subsequent doses of HD-MTX as eligibility and slots permitted. MTX 3.5 g/m² was administered once over 2 hours, preceded by standard hydration and followed by an additional 2 hours of dextrose 5% in water with NaHCO₃ 75 mEq at 150 cc/h. Glucarpidase 2000u was administered once in the clinic 24 hours later. The primary end point was MTX level 48 hours after HD-MTX.

Twenty doses of outpatient HD-MTX with glucarpidase were administered to seven patients. After 20 of 20 (100%) treatments, serum MTX levels were reduced to <100 nmol/L. Treatments were well-tolerated, and no admissions were required. One patient received additional outpatient hydration for elevated creatinine. Development of antiglucarpidase antibody was rare and did not affect treatment.

Outpatient HD-MTX with glucarpidase is safe and well-tolerated and has the potential to alter standard treatment for CNS lymphoma.