Recombinant Erwinia asparaginase in pediatric and young adult patients with ALL

The ALL Hub was pleased to speak with Luke Maese, pediatric hematologist oncologist at the University of Utah Huntsman Cancer Institute and Primary Children's Hospital, Salt Lake City, US. We asked, What are the clinical considerations for the use of recombinant Erwinia asparaginase in pediatric and young adult patients with acute lymphoblastic leukemia (ALL)?

Key learnings

• Asparagine plays a key role in ALL pathogenesis, and asparagine depletion is important in the treatment of ALL.¹
• Up to 30% of patients will develop hypersensitivity to E.coli-derived asparaginase and pediatric and young adult patients with ALL who do not receive a full course of asparaginase are at greater risk of relapse.¹
• JZP-458 is a recombinant Erwinia asparaginase indicated as a component of a multi-agent chemotherapeutic regimen for use in patients aged ≥1 month with ALL or lymphoblastic lymphoma who have developed hypersensitivity to E. coli-derived asparaginase.² It is primarily utilized when patients have hypersensitivity, anaphylactic, or allergic reactions to a pegylated form of E. coli-derived asparaginase.
• Pegylated asparaginase is used in the majority of consortiums and clinical trials and in the first-line for patients with ALL. However, patients may have hypersensitivity, allergic, or anaphylactic reactions.
  • In these cases, rechallenge with an asparaginase product derived from the same bacteria is not recommended.
  • It is then necessary to switch formulations to an asparaginase product derived from a different bacterial antigen; in the case of JZP-458, Erwinia.
• JZP-458 was investigated in the Children's Oncology Group AALL1931 study (NCT04145531) in patients who had hypersensitivity reactions as a part of their treatment and was found to be effective at depleting asparagine, with adequate asparaginase activity levels, in children and young adults with ALL.¹
• JZP-458 use in the United States and Canada:
  • Within the Children's Oncology Group and Dana Farber and St. Jude Consortium Institutions, JZP-458 is now the primary choice when a patient has hypersensitivity to pegylated E. coli-derived asparaginase.
  • There is no access to other Erwinia-based products in these regions.
• JZP-458 use in Europe/the EU:
  • In addition to JZP-458, which is approved by the European Medicines Agency (EMA), the EU have access to an additional Erwinia-based asparaginase, providing a choice of agents to use when patients have hypersensitivity reactions to E. coli-derived asparaginase.
• Dosing regimens are an important consideration. Several regulatory approved dosing regimens are available in both the US and Europe:
  • In the US, dosing may be every 48 hours, or Monday, Wednesday, Friday dosing, with differential administration of amounts of drug.
  • In Europe, the EMA permits similar use, but with the additional flexibility of intravenous as well as intramuscular administration (intravenous administration is not currently approved in the US).^2,3
• In summary, JZP-458 is used in patients with ALL who have allergic, hypersensitivity, or anaphylactic reactions to pegylated asparaginase and is effective in depleting asparagine, with the advantage of flexible administration and scheduling for providers and patients.

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