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Clinical Policy Bulletin:
Erwinaze (asparaginase Erwinia chrysanthemi)
Number: 0864


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.

CPT Codes / HCPCS Codes / ICD-9 Codes
Other CPT codes related to the CPB:
96401 Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
HCPCS codes covered if selection criteria are met:
J9019 Injection, asparaginase, (Erwinaze), 1,000 iu
Other HCPCS codes related to the CPB:
J9020 Injection, asparaginase, not otherwise specified, 10,000 units [Elspar]
J9266 Injection, pegaspargase, per single dose vial [Oncaspar]
ICD-9 codes covered if selection criteria are met:
204.00 - 204.02 Acute lymphoid leukemia [lymphoblastic]
ICD-9 codes not covered for indications listed in the CPB:
200.00 - 203.82 Lymphosarcoma and reticulosarcoma and other specified malignant tumors of lymphatic tissue [excluding ALL]
204.10 - 204.92 Malignant neoplasm of lymphatic and hematopoietic tissue [excluding ALL]
ICD-9 codes contraindicated for this CPB:
434.00 - 434.01 Cerebral thrombosis
444.21 - 444.22 Embolism and thrombosis of arteries of the extremities
452 Portal vein thrombosis
453.0 - 453.9 Other venous embolism and thrombosis
577.0 - 577.1 Pancreatitis
995.27 Other venous embolism and thrombosis

The above policy is based on the following references:
  1. EUSA Pharma (USA), Inc. Erwinaze (asparaginase Erwinia chrysanthemi) for injection, intramuscular use. Prescribing Information. Langhorne, PA: EUSA Pharma; revised November 2011.
  2. National Comprehensive Cancer Network (NCCN). Acute lymphoblastic leukemia. NCCN Clinical Practice Guidelines in Oncology, v.1.2012. Fort Washington, PA: NCCN; 2012.
  3. Moscardo Guilleme C, Fernandez Delgado R, Sevilla Navarro J, et al. Update on L-asparaginase treatment in paediatrics. An Pediatr (Barc). 2013;79(5):329.e1-329.e11.
  4. Salzer WL, Asselin B, Supko JG, et al. Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: A report from the Children's Oncology Group. Blood. 2013;122(4):507-514.
  5. Keating GM. Asparaginase Erwinia chrysanthemi (Erwinaze®): A guide to its use in acute lymphoblastic leukemia in the USA. BioDrugs. 2013;27(4):413-418.
  6. Emadi A, Zokaee H, Sausville EA. Asparaginase in the treatment of non-ALL hematologic malignancies. Cancer Chemother Pharmacol. 2014;73(5):875-883.

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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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