Patients with acute lymphoblastic leukemia (ALL) receiving Escherichia coli (E. coli)-derived asparaginase who develop hypersensitivity reactions (HSRs) or silent inactivation should switch to a non-E. coli-derived asparaginase, according to research published in Future Oncology.
Asparagine, which is necessary for protein synthesis and normal cell growth, is required by leukemia cells for growth and proliferation. For leukemia cells to successfully grow, however, extracellular asparagine is necessary, which is not true for healthy cells.
The discovery that extracellular asparagine is essential for leukemic growth led to the investigation and consequent introduction of therapeutic asparaginase for the treatment of hematologic malignancies, including ALL. Asparaginase therapy is, however, linked with both HSRs and reduced clinical efficacy over time.
In this paper, researchers explored the causes, clinical importance of, and potential guidance around HSRs among patients with ALL being treated with asparaginase.
HSRs are, according to the authors, found in up to 30% of patients who receive E. coli-derived asparaginase, 24% of patient who receive polyethylene glycol-asparaginase, and 37% of patients who receive Erwinia asparaginase. They can include localized erythema, urticaria, and systemic anaphylaxis, and are the most frequent cause of asparaginase treatment discontinuation.
HSRs may, furthermore, suggest the development of anti-asparaginase antibodies, which can lead to reduced clinical efficacy and overall survival.
Although the authors noted that switching asparaginase therapy may be necessary on development of HSRs or silent inactivation, premedication with antihistamines or corticosteroids may mitigate some effects of HSRs.
The researchers also noted that the recent US Food and Drug Administration approval of recombinant Erwinia asparaginase may help to alleviate any supply-related issues when switching treatments becomes necessary.
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Burke MJ, Zalewska-Szewczyk B. Hypersensitivity reactions to asparaginase therapy in acute lymphoblastic leukemia: immunology and clinical consequences. Future Oncol. Published online February 2, 2021. doi:10.2217/fon-2021-1288