Effects of L‐Asparaginase on Plasma Amino Acid Profiles and Tumor Burden in Cats with Lymphoma

Abstract

Background: L‐Asparaginase (Elspara), is anEscherichia coli‐derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L‐asparaginase on plasma amino acid concentrations is unknown.Hypotheses: L‐Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats.Animals: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L‐asparaginase for initial LSA treatment.Methods: Plasma collected at 0, 2, and 7 days after L‐asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response.Results: Eight cats had T‐cell LSA, 4 cats had B‐cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L‐asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged.Conclusions and Clinical Importance: L‐Asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L‐asparaginase in this study was 30%.