Aetna considers Erwinaze (asparaginase Erwinia chrysanthemi) medically necessary for persons with acute lymphoblastic leukemia (ALL) who are hypersensitive to Elspar (asparaginase Escherichia coli) or Oncaspar (pegaspargase).

Continued use beyond 3 months is considered medically necessary for persons with no evidence of disease progression relative to pre-treatment state.

Aetna considers Erwinaze experimental and investigational for persons with any of the following contraindications:

• Persons with a history of serious pancreatitis with prior L-asparaginase therapy
• Persons with a history of thrombosis with prior L-asparaginase therapy
• Persons who are hypersensitive to Erwinaze.

Aetna considers Erwinaze experimental and investigational for the treatment of non-ALL malignant blood disorders because its effectiveness for these indications has not been established.

Emadi et al (2014) stated that asparaginases are among the most effective agents against acute lymphoblastic leukemia (ALL) and are Food and Drug Administration (FDA)-approved for the treatment of pediatric and adult ALL.  However, the effectiveness of these drugs for the treatment of other hematologic malignancies particularly acute myeloid leukemia (AML) is not well-established.  The mechanism of action of asparaginases has thought to be related to a swift and sustained reduction in serum L-asparagine, which is required for rapid proliferation of metabolically demanding leukemic cells.  However, asparagine depletion alone appears not to be sufficient for effective cytotoxic activity of asparaginase against leukemia cells, because glutamine can rescue asparagine-deprived cells by regeneration of asparagine via a transamidation chemical reaction.  For this reason, glutamine reduction is also necessary for full anti-leukemic activity of asparaginase.  Indeed, both Escherichia coli and Erwinia chrysanthemi asparaginases possess glutaminase enzymatic activity, and their administrations have shown to reduce serum glutamine level by deamidating glutamine to glutamate and ammonia.  Emerging data have provided evidence that several types of neoplastic cells require glutamine for the synthesis of proteins, nucleic acids, and lipids.  This fundamental role of glutamine and its metabolic pathways for growth and proliferation of individual malignant cells may identify a special group of patients whose solid or hematologic neoplasms may benefit significantly from interruption of glutamine metabolism.  The authors stated that asparaginase products deserve a second look particularly in non-ALL malignant blood disorders.