CLINICAL MEDICAL POLICY Granulocyte Colony Stimulating Factors Policy Name: (G-CSFs: Neupogen, Granix) Policy Number: MP-016-MD-PA Responsible Department(s): Medical Management; Clinical Pharmacy Provider Notice Date: 08/15/2017 Original Effective Date: 09/15/2017 Annual Approval Date: 07/15/2018 Revision Date: N/A Products: Gateway Health℠ Medicaid Application: All participating hospitals and providers Page Number(s): 1 of 33 DISCLAIMER Gateway Health℠ (Gateway) medical policy is intended to serve only as a general reference resource regarding coverage for the services described. This policy does not constitute medical advice and is not intended to govern or otherwise influence medical decisions. POLICY STATEMENT Gateway Health℠ provides coverage under the medical or pharmacy benefits of the Company’s Medicaid products for medically necessary Granulocyte Colony Stimulating Factor (G-CSF) such as Neupogen, Granix. This policy is designed to address medical necessity guidelines that are appropriate for the majority of individuals with a particular disease, illness or condition. Each person’s unique clinical circumstances warrant individual consideration, based upon review of applicable medical records. (Current applicable Pennsylvania HealthChoices Agreement Section V. Program Requirements, B. Prior Authorization of Services, 1. General Prior Authorization Requirements.) Policy No. MP-016-MD-PA Page 1 of 33 DEFINITIONS Filgrastim - a recombinant granulocyte colony stimulating factor (rG-CSF). Colony Stimulating Factors – CSFs are naturally occurring cytokine glycoproteins classified as immunomodulators. They serve as growth factors specifically for myeloid hematopoietic cells Granulocyte Colony Stimulating Factor – G-CSF specifically modulates neutrophils and their precursors, regulating their production within the bone marrow and affecting neutrophil progenitor proliferation, differentiation and selected end-cell functional activation. Neutropenia – A hematological disorder characterized by an abnormally low number of neutrophil granulocytes. Febrile Neutropenia – A condition in which there is a temperature of approximately 38.5° (greater than 101°F) or greater, sustained for more than one hour, and developing concurrently with absolute neutropenia of less than 500 cells/µL. PROCEDURES 1. Medical Necessity Criteria A. Coverage for Neupogen and Granix as Granulocyte Colony Stimulating Factors (G-CSFs) is provided when the following medical necessity criteria are met in the use of G-CSFs as either primary prophylaxis or in the treatment of a member at risk for, or diagnosed with, neutropenia as a result of: 1) Neutropenia due to chemotherapy agents 2) Neutropenia due to radiotherapy agents 3) Neutropenia due to malignancy 4) Neutropenia due to AIDS/HIV 5) Neutropenia due to myelodysplasia 6) Severe chronic neutropenia (i.e., cyclic neutropenia, congenital neutropenia or idiopathic neutropenia) 7) BMT (bone marrow transplant) 8) Current or post-peripheral blood progenitor cell (PBPC) mobilization/transplantation 9) Neutropenia due to acute leukemia (AML and ALL) 10) Neutropenia due to Peginterferon therapy in a member with Hepatitis C when the ANC is ≤ 250/mm3 OR ANC is ≤ 500/mm3 with one of the following risk factors: cirrhosis, pre- or post-liver transplant, or HIV/HCV coinfection 11) Severe chronic congenital neutropenia B. Coverage is provided for secondary prevention of chemotherapy-related neutropenia (situation where the member has previously experienced neutropenia from chemotherapy agents). C. Coverage is provided for primary prevention of chemotherapy related to neutropenia (i.e., members who have not previously developed neutropenia from chemotherapy agents) in situations where the member may be at high risk for developing chemotherapy-induced neutropenia, such as: 1) Having advanced cancer; OR 2) Decreased immune function; OR Policy No. MP-016-MD-PA Page 2 of 33 3) A condition causing decreased bone marrow production; OR 4) An open wound; OR 5) An active infection; OR 6) Use of a medication known to cause neutropenia Note: For Neulasta, the member should not be receiving the medication during the period beginning 14 days before and ending 24 hours after administration of chemotherapy. 2. Contraindications A. Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. B. Neupogen and Neulasta are contraindicated in members with known hypersensitivity to E coli-derived proteins‚ filgrastim‚ or any component of the product. C. Granix has no labeled contraindications. D. Zarxio™ is contraindicated in members with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim products. E. All other Granulocyte Colony Stimulating Factor services require documentation of intolerance or failure with Neupogen or Granix in addition to meeting the criteria outline above. 3. When the administration of G-CSF is not covered The administration of G-CSF is not covered for conditions other than those listed above because the scientific evidence has not been established. Coverage may be provided for any non-FDA labeled indication if it is determined that the use is a medically accepted indication supported by nationally recognized pharmacy compendia or peer- reviewed medical literature for treatment of the diagnosis(es) for which it is prescribed. These requests will be reviewed on a case-by-case basis to determine medical necessity. When criteria are not met, the request will be forwarded to a Medical Director for review. The physician reviewer must override criteria when, in their professional judgment, the requested medication is medically necessary. 4. Post-payment Audit Statement The medical record must include documentation that reflects the medical necessity criteria and is subject to audit by Gateway Health℠ at any time pursuant to the terms of your provider agreement. 5. Place of Service The place of service for the administration of Granulocyte Colony Stimulating Factor is outpatient. Policy No. MP-016-MD-PA Page 3 of 33 GOVERNING BODIES APPROVAL Summary of FDA Approved Labeled Indications for G-CSF Products: Myelosuppressive Acute Myeloid Bone Progenitor Sever Chemotherapy Leukemia Marrow Cell Collection Chronic Transplant Neutropenia Neupogen® X X X X X Neulasta® X Granix® X Zarxio™ X X X X X CODING REQUIREMENTS Procedure Codes CPT/HCPCS Code Description J1442 Injection, filgrastim (G-CSF), excludes biosimilars, 1 microgram (Neupogen) J1447 Injection, tbo-filgrastim, 1 microgram (Granix) J2505 Injection, pegfilgrastim, 6 mg (Neulasta) J2820 Injection, sargramostim (GM-CSF), 50 mcg (Neulasta) Q5101 Injection, filgrastim (G-CSF), biosimilar, 1 mcg (Zarxio) Diagnosis Codes ICD-10 Codes Description B20 Human immunodeficiency virus, (HIV) disease C00.0 Malignant neoplasm of external upper lip C00.1 Malignant neoplasm of external lower lip C00.2 Malignant neoplasm of external lip, unspecified C00.3 Malignant neoplasm of upper lip, inner aspect C00.4 Malignant neoplasm of lower lip, inner aspect C00.5 Malignant neoplasm of lip, unspecified, inner aspect C00.6 Malignant neoplasm of commissure of lip, unspecified C00.8 Malignant neoplasm of overlapping sites of lip C00.9 Malignant neoplasm of lip, unspecified C01 Malignant neoplasm of base of tongue C02 Malignant neoplasm of other and unspecified parts of tongue C02.0 Malignant neoplasm of dorsal surface of tongue C02.1 Malignant neoplasm of border of tongue C02.2 Malignant neoplasm of ventral surface of tongue C02.3 Malignant neoplasm of anterior two-thirds of tongue, part unspecified C02.4 Malignant neoplasm of lingual tongue C02.8 Malignant neoplasm of overlapping sites of tongue C02.9 Malignant neoplasm of tongue, unspecified C03 Malignant neoplasm of gum C03.0 Malignant neoplasm of upper gum C03.1 Malignant neoplasm of lower gum C03.9 Malignant neoplasm of gum, unspecified Policy No. MP-016-MD-PA Page 4 of 33 C04 Malignant neoplasm of floor of mouth C04.0 Malignant neoplasm of anterior floor of mouth C04.1 Malignant neoplasm of lateral floor of mouth C04.8 Malignant neoplasm of overlapping sites of floor of mouth C04.9 Malignant neoplasm of floor of mouth, unspecified C05 Malignant neoplasm of palate C05.0 Malignant neoplasm of hard palate C05.1 Malignant neoplasm of soft palate C05.2 Malignant neoplasm of uvula C05.8 Malignant neoplasm of overlapping sites of palate C05.9 Malignant neoplasm of palate, unspecified C06 Malignant neoplasm of other and unspecified parts of mouth C06.0 Malignant neoplasm of cheek mucosa C06.1 Malignant neoplasm of vestibule of mouth C06.2 Malignant neoplasm of retro molar area C06.8 Malignant neoplasm of overlapping sites of other and unspecified parts of mouth C06.80 Malignant neoplasm of overlapping sites of unspecified parts of mouth C06.89 Malignant neoplasm of overlapping sites of other parts of mouth C06.9 Malignant neoplasm of mouth, unspecified C07 Malignant neoplasm of parotid gland C08 Malignant neoplasm of other and unspecified major salivary glands C08.0 Malignant neoplasm of submandibular gland C08.1 Malignant neoplasm of sublingual gland C08.9 Malignant neoplasm of major salivary gland, unspecified C09 Malignant neoplasm of tonsil C09.0 Malignant neoplasm of tonsillar fossa C09.1 Malignant neoplasm of tonsillar pillar (anterior) (posterior) C09.8 Malignant neoplasm of overlapping sites of tonsil C09.9 Malignant neoplasm of tonsil, unspecified C10 Malignant neoplasm of oropharynx C10.0 Malignant neoplasm