Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management

Abstract

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

RETRACTED: Peg-Asparaginase-Associated Pancreatitis in Chemotherapy-Treated Pediatric Patients: A 5-Year Retrospective Study

“…The manifestations of AAP was closely related to the pharmacokinetic characteristics of peg-asp. The half-life (5.7 days) of peg-asp was relatively longer than that of the other asparaginase formulations (6). The enzymatic activity could last for 18-21 days or more after administering a single dose of pegasp (17).…”

“…As suggested in recent ALL guidelines, severe AAP patients (severe pancreatitis with amylase elevation >3 times the UNL, accompanied with pseudocyst within 48 hours) were not allowed to receive any asparaginase as a prospective chemotherapy regimen (6,22). This definition is based on the revised Atlanta criteria (2012), which is a classification system for adults.…”

“…Peg-asparaginase (peg-asp) has a polyethylene glycol molecule conjugated to its E. coli-derived L-asparaginase (l-asp), which could alter its immunogenic property, preventing hypersensitivity and unfavorable immune response (5). With a longer half-life and better patient tolerance, peg-asp is now approved as a first-line asparaginase formulation in ALL chemotherapy regimens (6)(7)(8). Others recommend peg-asp as an alternative treatment for ALL patients who are hypersensitive to native asparaginase (9).…”

“…Asparaginaseassociated pancreatitis (AAP) is one of the most common adverse events. The onset of severe AAP would require permanent withdrawal of asparaginase from the patient's chemotherapy regimen, which affected the remission rate and resulted in a poor treatment outcome (6). Studies regarding pediatric peg-asp-associated pancreatitis are limited.…”

Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia

“…Our toxicity data support the safety of using pegaspargase as part of the HAM-pegA regimen in an adult population (age >40 years old), as there were no clinically significant differences in adverse events when compared to CLAG-M. Additionally, the literature currently available regarding pegaspargase-related toxicities is limited to the ALL population, however it is possible that the toxicity profile may be different in an AML population. Our institution has recently developed and implemented guidelines for the prevention, monitoring, and management of pegaspargase-related adverse events to further ensure tolerability of pegaspargase in adults, including older adults [9]. Of note, since the adoption of these institutional pegaspargase guidelines, our institution now limits the pegaspargase dose to a maximum of 3750 units for all patients >18 years old.…”