CTNI-57. PLANNED-USE GLUCARPIDASE FOR OUTPATIENT HIGH DOSE METHOTREXATE (HD-MTX) IN PATIENTS WITH CNS LYMPHOMA

Abstract INTRODUCTION HD-MTX is standard treatment for central nervous system lymphoma (CNSL). Administration typically requires hospitalization until drug clearance, due to toxicity risks. We previously demonstrated that glucarpidase, a bacterial recombinant enzyme that rapidly degrades MTX, facilitated outpatient MTX treatments during the COVID-19 pandemic. Here, we further assess feasibility of outpatient MTX with planned glucarpidase use. METHODS This prospective, non-randomized study included two cohorts. Cohort A received eight 14-day cycles of MTX 3.5 g/m2 and glucarpidase 2000u 24 hours later. Cohort B included rituximab 500 mg/m2, and 1000u glucarpidase in cycles 3-8 only. In both cohorts, cycles 1-2 were administered inpatient to ensure MTX tolerability, while cycles 3-8 were outpatient. Concurrent chemo/targeted therapies were permitted at physician discretion. The primary endpoint was serum MTX reduction 1 hour after glucarpidase. Patients not receiving at least 6 cycles of glucarpidase were replaced. RESULTS Eighteen patients consented (Cohort A: 4; Cohort B: 14). Twelve transitioned to outpatient MTX with glucarpidase; six disenrolled before outpatient treatment due to preference or elevated creatinine. Median age was 73.5 (range, 44-82), median Karnofsky Performance Status (KPS) 80 (range, 60-90). One Cohort B patient withdrew after the first outpatient cycle due to preference. Remaining Cohort B patients completed all planned cycles. No hospital admissions or MTX dose-reductions occurred. Median MTX reduction 1 hour post-glucarpidase was 99.6% (range, 62.2-100%). Reduced clearance was noted in one Cohort A and three Cohort B patients; antibody analysis is ongoing. Treatment was well tolerated with no grade 3/4 adverse events attributed to glucarpidase. One Cohort A patient experienced a grade 2 allergic reaction. Grade 1 events included dizziness, fatigue (n=2), flushing, headache, infusion reaction, nausea, paresthesia, pruritus, and rash. CONCLUSIONS Planned-use glucarpidase enables safe and feasible outpatient MTX administration in healthy patients who have previously tolerated MTX.