10119- COT-12 ROLE OF GLUCARPIDASE IN DELAYED METHOTREXATE EXCRETION, BASED ON OUR EXPERIENCE

Abstract INTRODUCTION High-dose methotrexate (HD-MTX) is widely used to treat primary central nervous system lymphomas and medulloblastoma in infants. A key problem associated with this regimen is slow elimination, which can rapidly cause renal and hepatic damage. Glucarpidase was launched in January 2024 as a treatment for delayed elimination, but to date no guidelines have been established for its administration in Japan. Thus, we retrospectively examined data from cases of glucarpidase use in our department, including patients enrolled in the clinical trial. PATIENTS AND METHODS This study included 14 patients (10 males and four females) who received glucarpidase to counter delayed elimination during HD-MTX therapy between January 2015 and July 2024. RESULTS Median patient age was 7.5 years (range: 1.5-79 years) and the treated disease was acute leukemia in seven patients, lymphoma in four, osteosarcoma in two, and medulloblastoma in one. During glucarpidase administration, seven patients were experiencing renal impairment and three had elevated hepatic enzyme levels. The median blood MTX concentration at the first dose of glucarpidase was 4.9 μM (range: 1.02-24.1 μM). This decreased to 0.22 μM (range: 0.07-1.66 μM) at 48 h post-administration. Glucarpitase was re-administered in one patient. Median time to <0.2 μM was 96 h (range: 24-336 h). Peak renal impairment occurred at a median of 24 h (range: 0-96 h), and median time to normalization was 456 h (range: 96-648 h). Six of 12 patients were re-treated with HD-MTX. Four of these showed delayed elimination but did not require glucarpidase re-administration. DISCUSSION This study confirmed the efficacy and safety of glucuronidase for delayed elimination during HD-MTX therapy in real-world clinical practice. Timely detection of delayed elimination and examination of the indications for this agent are important to improve HD-MTX therapy safety.