A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high‐dose methotrexate therapy in open‐label trials

Abstract

AbstractBackgroundDelayed methotrexate elimination can occur in patients undergoing high‐dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate‐use trials in patients aged 0–84 years.MethodsWe performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open‐label, single‐arm, glucarpidase compassionate‐use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 μmol/L at all post‐glucarpidase measurements) based on high‐performance liquid chromatography.ResultsAmong 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post‐glucarpidase. Patients with pre‐glucarpidase methotrexate less than 50 μmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 μmol/L or higher (1/37, 2.7%). The most common treatment‐related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment‐related adverse event occurred in 5% or higher of any age group.ConclusionAfter accounting for pre‐glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0–84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well‐tolerated dose for pediatric, adolescent, and young adult patients.