How to optimize dosing regimens for recombinant asparaginase in ALL?

The ALL Hub spoke with Wendy Stock, The University of Chicago, Chicago, US. We asked, How to optimize dosing regimens for recombinant asparaginase in acute lymphoblastic leukemia (ALL)?

In this interview, Wendy Stock discusses the challenges of managing asparaginase treatment in adults with ALL. Stock highlights the effectiveness of the therapy in younger adults but notes the difficulties of optimizing asparaginase dosing and managing associated toxicities, including hepatic issues, thrombosis, and pancreatitis. Stock points out the lack of formal guidelines and underscores the need for further research, including therapeutic drug monitoring and studies on anticoagulation. Ongoing studies aim to improve understanding of the risk factors for experiencing adverse events and how to optimize treatment approaches for better patient outcomes.

 Key learnings

• The introduction of asparaginase has resulted in improved outcomes, particularly for young adults with ALL. However, dosing asparaginase can be challenging in certain populations, including older adults, due to its associated toxicities and the lack of formal guidelines.
• There are a lack of data to identify whether current asparaginase dosing is appropriate or too high, and more research, particularly with therapeutic drug monitoring, is needed to tailor dosing appropriately.
• Common toxicities associated with asparaginase treatment include hepatic toxicity, transaminitis, and hyperbilirubinemia. Serious toxicities involve thrombosis, particularly sagittal vein thrombosis, and pancreatitis. 
• Where serious pancreatitis occurs, patients cannot be retreated with asparaginase.
• Preventing and managing toxicities is complex because it is hard to predict who will develop a toxicity. Therapeutic monitoring and initiating treatment with lower doses in patients with hepatic dysfunction, diabetes, or who are morbidly obese may help to reduce toxicity, but prospective studies are needed.
• Addressing thrombotic events, particularly in the first few months of treatment, is important. There are no formal anticoagulation guidelines and individual centers approach anticoagulation differently, such as using antithrombin monitoring or prophylactic enoxaparin.
• Despite ongoing research, formal guidelines for asparaginase management, including anticoagulation and toxicity management, are lacking, highlighting the need for more data on these topics.
  • The American Society of Hematology (ASH) is creating new clinical practice guidelines for treating adolescents and young adults with ALL, as part of the ASH Clinical Practice Guidelines on Acute Lymphoblastic Leukemia.

This educational resource is independently supported by Jazz Pharmaceuticals. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.