Asparaginase Activity Levels and Tolerability Following Intravenous Pegaspargase in Adults with Acute Lymphoblastic Leukemia Receiving Multi-Agent Chemotherapy

Abstract

Background: Therapeutic drug monitoring (TDM) has emerged as an important monitoring tool for adults with acute lymphoblastic leukemia (AAL) receiving pegaspargase. For adequate asparagine depletion in leukemia cells, nadir asparaginase activity levels (AALs) are targeted to be ≥0.1 units/mL. AALs achieved following ongoing TDM and dose adjustments of pegaspargase have not yet been reported in adults. Objectives: The primary objective was to describe longitudinal TDM of AALs for patients receiving pegaspargase and the secondary objective was to describe tolerability. Methods: This was a single centre retrospective chart review including 26 patients ≥18 years who received intravenous pegaspargase as part of a chemotherapy protocol for AAL between December 2017 and November 2018. Phases of treatment included one dose of pegaspargase during induction and 7 – 10 doses every 21 days during intensification. AAL monitoring was scheduled for 15 and 22 days after each administration of pegaspargase. Results: In total, 115 doses of pegaspargase were given and 203 AALs were analyzed. Of 17 AALs (n = 17) measured during induction 22 days after pegaspargase administration, only 3 (18%) were ≥ 0.1 units/mL. During intensification, of 53 nadir AALs (n = 11), 47 (89%) were ≥ 0.1 units/mL at a variety of different individualized doses ranging from 550 to 2000 units/m2. The most common adverse effects were grade 3 and 4 elevated transaminases (38%), bilirubin increases (31%), and hypertriglyceridemia (15%). Conclusion: TDM and individualized dosing of pegaspargase given every 21 days appears feasible for adult patients to achieve and maintain target nadir AALs.