Understanding and Overcoming Toxicities in Asparaginase Treatment for ALL

Because asparaginase is used exclusively in ALL, most adult oncologists do not administer it routinely.

There are many different uses for asparaginase and it is important to understand each of the toxicities that can arise from treatment, according to a presentation at the Society of Hematologic Oncology (SOHO) 2021 Annual Meeting.

Ibrahim T. Aldoss, MD, City of Hope Comprehensive Cancer Center, Duarte, California, went into detail on the use of asparaginase, a bacterial-derived enzyme, and how it is a key element in pediatric-inspired regimens in adolescent and young adult (AYA) acute lymphocytic leukemia (ALL).

“The efficacy of asparaginase correlates with maintaining adequate and prolonged depletion of serum asparagine,” Aldoss said. “Further, inadequate dosing and early discontinuation as the result of toxicity were associated with inferior outcomes.”

Because asparaginase is used exclusively in ALL, most adult oncologists do not administer it routinely. Aldoss explained that each patient’s toxicity profile is unique and more common with age, and each toxicity—especially if it is biochemical—can be perceived as severe.

Hypersensitivity occurs as an immune response from asparaginase and any clinical or silent hypersensitivity can lead to drug inactivation.

“The risk factors can occur in children, in addition to no concurrent use of rituximab, or not using pre-meds,” Aldoss said.

If these needs to be managed, Aldoss added that switching to an Erwinia-based asparaginase could be the best treatment.

The most common toxicity, hepatotoxicity, is high-grade and can result in early interruption in therapy, compromising therapy efficacy in some cases. This is observed in early cycles, and the risk factors include older age, obesity, re4880 polymorphism, and higher drug doses, according to Aldoss.

“Hepatotoxicity is not an indication to discontinue subsequent asparaginase doses, even at higher grades,” Aldoss said.

Prevention includes recusing the dosage for patients who are older and obese, and making the asparaginase dose at 1 vial.

Thrombosis and pancreatitis are also commonly observed, according to Aldoss, and each carries its own risks based on specific factors. Early diagnosis and treatment are key for pancreatitis, with Aldoss recommending against Erwinase use as a replacement for clinical pancreatitis. In terms of thrombosis, older age, obesity, and replacement with cryoprecipitate can be major risks, with venous thromboembolism (VTE) being a common treatment after the first 2 doses of asparaginase.

“If VTE occurs, start anticoagulation,” Aldoss said. “VTE recurrence is uncommon in patients on anticoagulation when asparaginase is resumed, and this is not an indication to hold subsequent asparaginase therapy.”

Some other metabolic abnormalities include hypertriglyceridemia and hypofibrinogenemia, which are the most common, as well as hyperammonemia and hyperglycemia.

REFERENCE

Aldoss IT. Asparaginase: Understanding and Overcoming Toxicities. Presented at: the Society of Hematologic Oncology (SOHO) 2021 Annual Meeting; virtual. September 8, 2021. Accessed September 9, 2021.