CLINICAL MEDICATION POLICY Policy Name: Granulocyte Colony Stimulating Factors (G-CSFs: Neupogen®, Granix®, Neulasta ®, Zarxio ®) Policy Number: MP-006-MC-ALL Responsible Departments: Medical Management; Clinical Pharmacy Provider Notice Date: 12/15/2018; 12/15/2017; 04/01/2017 Issue Date: 01/15/2019 Original Effective Date: 01/15/2019; 01/15/2018; 05/01/2017 Annual Approval Date: 11/14/2019 Revision Date: 11/14/2018; 11/08/2017 Products: Pennsylvania Medicare Assured Application: All participating and nonparticipating hospitals and providers Page Number(s): 1 of 29 DISCLAIMER Gateway HealthSM (Gateway) clinical medication 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℠ may provide coverage under the medical benefits of the Company’s Medicare products for medically necessary Granulocyte Colony Stimulating Factors (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. DEFINITIONS Filgrastim – A recombinant granulocyte colony stimulating factor (rG-CSF). Colony Stimulating Factors (CSFs) – CSFs are naturally occurring cytokine glycoproteins classified as immunomodulators. They serve as growth factors specifically for myeloid hematopoietic cells Policy No. MP-006-MC-ALL Page 1 of 29 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. The following G-CSFs are preferred: 1) Granix (tbo-filgrastim) B. All other G-CSFs are considered non-preferred and require documentation of failure with one of the preferred G-CSFs in addition to meeting the criteria outlined below: 1) Neupogen (filgrastim) 2) Neulasta (pegfilgrastim) 3) Fulphila (pegfilgrastim-jmdb_ 4) Zarxio (filgrastim-sndz) 5) Leukine (sargramostim) For all requests for Granulocyte Colony Stimulating Factors all of the following criteria must be met: All requests must be prescribed by, or in consultation with, an oncologist or hematologist The requested dose and frequency is in accordance with FDA-approved labeling, nationally recognized compendia, and/or evidence-based practice guidelines C. Coverage may be provided with a diagnosis of primary prophylaxis of febrile neutropenia (FN) and the following criteria are met: 1) Request must be for Neupogen (filgrastim), Zarxio (filgrastim-sndz), Neulasta (pegfilgrastim), Fulphila (pegfilgrastim-jmdb), or Granix (tbo-filgrastim) 2) Must also meet at least one of the following: i. Must have a solid tumor or non-myeloid malignancy and be receiving myelosuppressive chemotherapy which has a greater than 20% risk of FN, as indicated in current American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines for myeloid growth factors; ii. Must have a solid tumor or non-myeloid malignancy and be receiving nonmyelosuppressive chemotherapy which has 10-20% risk of FN, and be considered to be at high risk for chemotherapy-induced FN or infection due to at least one of the following: 1. Age greater than 65 years; 2. Poor performance status; 3. Previous episode of FN; 4. Extensive prior treatment including large radiation ports 5. Previous chemotherapy or radiation therapy 6. Preexisting neutropenia 7. Cytopenias due to bone marrow involvement by tumor Policy No. MP-006-MC-ALL Page 2 of 29 8. Poor nutritional status 9. Presence of open wounds or active infections 10. Recent surgery 11. Advanced cancer 12. Cardiovascular disease 13. Mucositis 14. Poor renal function 15. Liver dysfunction, most notably elevated bilirubin iii. Must be receiving a dose-dense chemotherapy regimen for the treatment of node- positive breast cancer, small-cell lung cancer, or diffuse aggressive non-Hodgkin’s Lymphoma. D. Coverage may be provided with a diagnosis of secondary prophylaxis of febrile neutropenia and the following criteria are met: 1) Request must be for Neupogen (filgrastim), Zarxio (filgrastim-sndz), Neulasta (pegfilgrastim), or Granix (tbo-filgrastim) 2) Member must have a documented episode of neutropenia from a prior cycle of chemotherapy for which primary prophylaxis was not received and a reduction in dose may compromise treatment outcome. E. Coverage may be provided for the mobilization of progenitor cells into peripheral blood for collection by leukophoresis and the following criteria is met: 1) Request must be for Neupogen (filgrastim), Leukine (sargramostim), or Zarxio (filgrastim-sndz). F. Coverage may be provided to reduce the duration of severe neutropenia following autologous stem-cell transplantation and the following criteria is met: 1) Request must be for Neupogen (filgrastim) or Zarxio (filgrastim-sndz) G. Coverage may be provided to reduce time to neutrophil recovery and duration of fever in adult patients with acute myeloid leukemia receiving induction or consolidation therapy and the following criteria is met: 1) Request must be for Neupogen (filgrastim) or Zarxio (filgrastim-sndz). H. Coverage may be provided with a diagnosis of congenital, cyclic, or idiopathic neutropenia and the following criteria are met: 1) Request must be for Neupogen (filgrastim) or Zarxio (filgrastim-sndz) 2) Must have experienced an infection requiring antibiotic treatment during the previous 12 months 3) For congenital or idiopathic neutropenia must have at least three documented episodes of severe chronic neutropenia (ANC <500/uL) during a 6 month period 4) For cyclic neutropenia must have documentation of 5 consecutive days of severe neutropenia (ANC <500/uL) per cycle. I. Coverage may be provided to increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) and the following criteria is met: 1) Request must be for Leukine (sargramostim), Neupogen (filgrastim) or Neulasta (pegfilgrastim). Policy No. MP-006-MC-ALL Page 3 of 29 J. Coverage may be provided for myeloid recovery following bone marrow transplant and the following criteria are met: 1) Request must be for Leukine (sargramostim) 2) Must meet one of the following criteria: i. Must have undergone allogenic bone marrow transplant from HLA-matched related donor ii. Must have undergone autologous bone marrow transplant for non-Hodgkin’s lymphoma, acute lymphoblastic leukemia, or Hodgkin’s disease iii. Must have failed or delayed engraftment post bone marrow transplant as defined below: 1. Delay in engraftment: ANC ≤ 100 cells/mm3 by day 28 posttransplantation OR ANC ≤ 100 cells/mm3 by day 21 posttransplantation with evidence of active infection 2. Engraftment failure: average of ANC ≥ 500 cells/mm3 for at least one week followed by loss of engraftment with ANC < 500 cells/mm3 for at least one week beyond day 21 post transplantation 2. 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. 3. 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. Coverage Determination Gateway Health ℠ follows the coverage determinations made by CMS as outlined in either the national coverage determinations (NCD) or the state-specific local carrier determination (LCD). There is no specific NCD or Pennsylvania LCD (Novitas Solutions, Inc.) for G-CSF. For additional information, please see: http://www.novitas- solutions.com/webcenter/portal/MedicalPolicy_JL/?_afrLoop=237596175793895#!%40%40%3F_afrLoo p%3D237596175793895%26_adf.ctrl-state%3Dwnoa115p2_42 Policy No. MP-006-MC-ALL Page 4 of 29 GOVERNING BODIES APPROVAL Summary of FDA Approved Labeled Indications for G-CSF Products: Myelosuppressive Acute Bone Progenitor Sever Chemotherapy Myeloid Marrow Cell Chronic Leukemia Transplant Collection Neutropenia Neupogen® X X X X X Neulasta® X Granix® X Zarxio™ X X X X X CODING REQUIREMENTS Procedure Codes HCPCS Codes Description J1442 Injection, filgrastim (G-CSF), excludes