Recognition, prevention, and management of adverse events associated with asparaginase/ pegaspargase treatment of acute lymphoblastic leukemia in adults: consensus of an expert panel

Abstract

Asparaginase (ASNase)-based chemotherapy regimens significantly improve survival outcomes in children, adolescents and young adults (AYA), and even adults with acute lymphoblastic leukemia/lymphoma (ALL); however, the incidence and severity of ASNase-associated adverse events (AE) in adults may differ significantly from those reported in children. Strategies to mitigate, monitor for, and manage toxicities that allow adult ALL patients to receive full ASNase courses are needed. A representative 12-member panel of experts who treat AYA and adult ALL patients, incorporate ASNase into their treatment regimens, and conduct related research was assembled to consider opportunities to optimize the use of pediatric-inspired ALL regimens in these adult patients. Following 2 systematic biomedical literature searches from April 2009 through April 2024, a modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus. After 2 iterative Delphi method surveys, 23 statements met the standardized definition of consensus, whereas 19 statements did not. Five statements were merged to avoid redundancy. The clinical statements were grouped into 5 distinct categories: 1) hepatotoxicity; 2) hypersensitivity reactions; 3) thromboembolic and coagulopathy complications; 4) pancreatitis and metabolic complications; and 5) dosing. The intent of these statements is to provide health care providers with information that will help them mitigate, monitor for, and manage the most common and/or unique ASNase-induced AE in adult ALL patients, allowing these patients to receive more or all the planned ASNase doses and thereby improve outcomes.

Figure 1.

Predetermined steps for consensus statement development. AE: adverse event; ALL: acute lymphoblastic leukemia; ASNase: asparaginase.

Figure 2.

Treatment algorithm following reaction to asparaginase-based therapy. Adapted with permission from Bleyer et al. CTCAE: Common Terminology Criteria for Adverse Events; HSR: hypersensitivity reaction; SAA: serum asparaginase activity.

Figure 3.

Clinical pathway to classification and management of adverse events to asparaginase. Adapted with permission from Burke et al. LLQ: lower limits of quantification; M/W/F: Monday / Wednesday / Friday; PEG: pegylated.

Figure 4.

Pegylated asparaginase therapeutic drug monitoring algorithm. Adapted with permission from Douer. PEG-ASNase: pegylated asparaginase; SAA: serum asparaginase activity.