CTNI-56. PLANNED GLUCARPIDASE FOR CNS LYMPHOMA PATIENTS AT HIGH RISK OF METHOTREXATE (MTX) TOXICITY

Abstract INTRODUCTION Methotrexate (MTX) is first-line treatment for central nervous system lymphoma (CNSL) but poses significant toxicity risks, especially in patients with renal dysfunction. Glucarpidase 50 u/kg is approved for treatment of MTX toxicity once it develops. Here, we aim to explore empiric glucarpidase administration for patients at high-risk of MTX toxicity. METHODS This is a prospective study of planned low-dose glucarpidase (1000u) following MTX in patients with CNSL. Eligible patients had baseline CrCl <60 ml/min, or history of delayed MTX clearance or grade 2 or higher MTX-related toxicity. Each enrollment corresponded to one MTX and glucarpidase dose; re-enrollment was permitted. Glucarpidase was given ≥ 24 hours post-MTX. The primary endpoint was MTX clearance (≤ 100 nmol/L) 24 hours following glucarpidase. This study is registered on clinicaltrials.gov (NCT03684980). RESULTS Twenty glucarpidase treatments were administered to 8 patients (6 men, 2 women) with a median age 72.5 (range, 53-83). The baseline Karnofsky Performance Status was 80 (range, 70-100). Enrollment indications included renal dysfunction (n=1), history of delayed MTX clearance (n=2), and MTX-related acute kidney injury (n=5). Patients enrolled one (n=5), four (n=2), or seven times (n=1). MTX levels were reduced to < 100 nmol/L 24 hours after glucarpidase following 17 of 20 treatments (85%). In the remaining 3 cases—occurring in the same patient — MTX levels were reduced by >97%. There were no events attributed to glucarpidase. There were five grade 3 events at least possibly attributed to MTX that included anemia (n=2), creatinine increase (n=1), and absolute lymphocyte count (ALC) decrease (n=2). Other MTX-attributed adverse events were grade 1 or 2. Anti-glucarpidase antibody data are pending. CONCLUSION Planned low-dose glucarpidase 1000u results in rapid MTX clearance in patients at high risk of MTX toxicity. Further research is needed to determine whether it prevents MTX dose-reduction, reduces toxicity, or shortens hospital admission.