Last Review Date: 03/31/2023

Date of Origin: 10/17/2008

Dates Reviewed: 06/2009, 12/2009, 06/2010, 07/2010, 09/2010, 12/2010, 03/2011, 06/2011, 09/2011, 12/2011, 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 04/2019, 04/2020, 04/2021, 04/2022, 04/2023

I. Length of Authorization

High Risk Neuroblastoma:

• When used in combination with dinutuximab, coverage will be provided for five months and may not be renewed.
• When used in combination with naxitamab, coverage will be provided for six months and may be renewed.

All other indications: Coverage will be provided for six months and may be renewed.

II. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Leukine 250 mcg vial: 28 vials per 14 days

2. Max Units (per dose and over time) [HCPCS Unit]:

• 15 billable units per day (acute radiation syndrome)
• 10 billable units per day on days 1 through 14 of cycles 1, 3 and 5 (cycle length is 24 days) for a maximum of 5 cycles only (high-risk neuroblastoma in combination with dinutuximab)
• 10 billable units per day for 10 days of each 28-day cycle for six cycles followed by subsequent cycles every 8 weeks thereafter (high-risk neuroblastoma in combination with naxitamab)
• 10 billable units per day (all other indications)

III. Initial Approval Criteria^1-11

Coverage is provided in the following conditions:

Myeloid reconstitution after autologous or allogeneic bone marrow transplant (BMT) †

Peripheral Blood Progenitor Cell (PBPC) mobilization and transplant †

Acute Myeloid Leukemia (AML) following induction or consolidation chemotherapy † Ф

Bone Marrow Transplantation (BMT) failure or Engraftment Delay † Ф

Treatment of chemotherapy-induced febrile neutropenia ‡

• Used for the treatment of chemotherapy induced febrile neutropenia in patients who have not received prophylactic therapy with a granulocyte colony stimulating factor; AND
• Patient has one or more of the following risk factors for developing infection-related complications:
  • • Sepsis Syndrome
    • Age greater than 65 years
    • Absolute neutrophil count [ANC] less than 100/mcL
    • Duration of neutropenia expected to be greater than 10 days
    • Pneumonia or other clinically documented infections
    • Invasive fungal infection
    • Hospitalization at the time of fever
    • Prior episode of febrile neutropenia

Patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome [H-ARS]) † Ф

High-Risk Neuroblastoma † ^12,13

• Used in combination with GD2-binding monoclonal antibodies (i.e., naxitamab, dinutuximab, etc.) for the treatment of high-risk neuroblastoma

† FDA-labeled indication(s); ‡ Compendia recommended indication(s); Ф Orphan Drug

IV. Renewal Criteria ^1,12,13

High-Risk Neuroblastoma

• Use in combination with dinutuximab may not be renewed.
• Used in combination with naxitamab; AND
  • Patient continues to meet indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
  • Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include severe hypersensitivity reactions, severe effusions and capillary leak syndrome, severe supraventricular arrythmias, etc.

All Other Indications

• Refer to initial prior authorization criteria.

V. Dosage/Administration^1-13

VI. Billing Code/Availability Information

HCPCS Code:

• J2820 – Injection, sargramostim (GM-CSF), 50 mcg: 1 billable unit = 50 mcg

NDC:

• Leukine 250 mcg single-dose vial: 00024-5843-xx

VII. References

1. Leukine [package insert]. Lexington, MA; Partner Therapeutics, Inc.; May 2022.  Accessed February 2023.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) sargramostim. National Comprehensive Cancer Network, 2023. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed February 2023.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Hematopoietic Growth Factors. Version 3.2022. National Comprehensive Cancer Network, 2023. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed February 2023.
4. Arora M, Burns LJ, Barker JN, et al. Randomized comparison of granulocyte colony-stimulating factor versus granulocyte-macrophage colony-stimulating factor plus intensive chemotherapy for peripheral blood stem cell mobilization and autologous transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2004;10(6):395-404.
5. Berghmans T, Paesmans M, Lafitte JJ, et al. Therapeutic use of granulocyte and granulocyte-macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis. Support Care Cancer. 2002;10(3):181-188.
6. Dubois RW, Pinto LA, Bernal M, et al. Benefits of GM-CSF versus placebo or G-CSF in reducing chemotherapy-induced complications: A systematic review of the literature. Support Cancer Ther. 2004;2(1):34-41.
7. Nemunaitis J, Rosenfeld CS, Ash R, et al. Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. Bone Marrow Transplant. 1995;15(6):949-954.
8. Nemunaitis J, Singer JW, Buckner CD, et al. Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation. Blood. 1990;76(1):245-253.
9. Nemunaitis J, Buckner CD, Appelbaum FR et al. Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Blood. 1991;77:2065-71.
10. Nemunaitis J, Rabinowe SN, Singer JW et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med. 1991;324:1773-8.
11. Rabinowe SN, Neuberg D, Bierman PJ et al. Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies. Blood. 1993;81:1903-8.
12. Rowe JN, Andersen JW, Mazza JJ et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457-62.
13. Danyelza [package insert]. New York, NY; Y-mAbs Therapeutics, Inc. ; November 2020.  Accessed December 2020.
14. Unituxin [package insert]. Silver Spring, MD; United Therapeutics Corp; September 2020.  Accessed December 2020.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Articles (LCAs), and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/ search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD): N/A