Last Review Date: 04/03/2019

Date of Origin: 08/06/2018

Dates Reviewed: 08/2018, 04/2019

1. Length of Authorization

Coverage will be provided for six months and may be renewed.

2. Dosing Limits

A.  Quantity Limit (max daily dose) [Pharmacy Benefit]:

• Nivestym 300 mcg vial: 3 vials per 1 day
• Nivestym 300 mcg prefilled syringe: 3 syringes per 1 day
• Nivestym 480 mcg vial: 3 vials per 1 day
• Nivestym 480 mcg prefilled syringe: 3 syringes per 1 day

B.  Max Units (per dose and over time) [Medical Benefit]:

• Severe Chronic Neutropenia:

• 1380 billable units per day

• BMT or PBPC or Radiation:

• 1200 billable units per day

• All other indications:

• 600 billable units per day

3. Initial Approval Criteria

Coverage is provided in the following conditions:

Bone marrow transplant (BMT) †

Peripheral Blood Progenitor Cell (PBPC) mobilization and transplant †

Prophylactic use in patients with non-myeloid malignancy †

• Patient is undergoing myelosuppressive chemotherapy with an expected incidence of febrile neutropenia of 20% or greater §; OR
• Patient is undergoing myelosuppressive chemotherapy with an expected incidence of febrile neutropenia of 10% or greater§ AND one or more of the following co-morbidities:

• Elderly patients (age 65 or older) receiving full dose intensity chemotherapy
• History of recurrent febrile neutropenia from chemotherapy
• Extensive prior exposure to chemotherapy
• Previous exposure of pelvis, or other areas of large amounts of bone marrow, to radiation
• Pre-existing neutropenia (ANC ≤ 1000/mm³)  or bone marrow involvement with tumor
• Patient has a condition that can potentially increase the risk of serious infection (i.e. HIV/AIDS)
• Infection/open wounds
• Recent surgery
• Poor performance status
• Poor renal function (creatinine clearance <50)
• Liver dysfunction (elevated bilirubin >2.0)
• Chronic immunosuppression in the post-transplant setting including organ transplant

Treatment of chemotherapy-induced febrile neutropenia ‡

• Used for the treatment of chemotherapy induced febrile neutropenia; AND
  • Patient has been on prophylactic therapy with filgrastim; OR
  • Patient has 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 >65
    • Absolute neutrophil count [ANC] <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

Patient who experienced a neutropenic complication from a prior cycle of the same chemotherapy ‡

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

Bone Marrow Transplantation (BMT) failure or Engraftment Delay ‡

Severe chronic neutropenia †

• Patient must have an absolute neutrophil count (ANC) < 500/mm³; AND
• Patient must have a diagnosis of one of the following:
  • Congenital neutropenia; OR
  • Cyclic neutropenia; OR
  • Idiopathic neutropenia

Myelodysplastic Syndromes (MDS) ‡

• Endogenous serum erythropoietin level of ≤500 mUnits/mL; AND
• Patient has lower risk disease (i.e., defined as IPSS-R [Very Low, Low, Intermediate], IPSS [Low/Intermediate-1], WPSS [Very Low, Low, Intermediate]); AND
• Used for treatment of symptomatic anemia in patients without del(5q); AND
• Patient is receiving concurrent therapy with an Erythropoiesis Stimulating Agent (ESA); AND
  • • Patient has ring sideroblasts < 15% and will use in combination with lenalidomide following no response (despite adequate iron stores) or loss or response to an ESA alone; OR
    • Patient has ring sideroblasts ≥ 15%

Patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome) ‡

Management of CAR T-cell related Toxicity ‡

• Patient has been receiving therapy with CAR T-cell therapy (e.g. tisangenleclecleucel (Kymriah), Axicabtagene Ciloleucel (Yescarta), etc.); AND
• Patient is experiencing neutropenia related to their therapy.

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

§ Expected incidence of febrile neutropenia percentages for myelosuppressive chemotherapy regimens can be found in the NCCN Myeloid Growth Factors Clinical Practice Guideline at NCCN.org.

4. Renewal Criteria

Same as initial prior authorization policy criteria.

5. Dosage/Administration

6. Billing Code/Availability Information

HCPCS Code:

• Q5110 –  Injection, filgrastim-aafi, biosimilar, (nivestym), 1 microgram. 1 billable unit = 1 microgram. 

NDC:

• Nivestym 300 mcg vial: 00069-0293-xx
• Nivestym 300 mcg prefilled syringe: 00069-0291-xx
• Nivestym 480 mcg vial: 00069-0294-xx
• Nivestym 480 mcg prefilled syringe: 00069-0292-xx

7. References

1. Nivestym [package insert]. Lake Forest, IL; Hospira Inc; July 2018. Accessed March 2019.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) filgrastim-aafi. National Comprehensive Cancer Network, 2019. 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 March 2019.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Hematopoietic Growth Factors. Version 1.2019.  National Comprehensive Cancer Network, 2019. 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 March 2019.
4. Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015 Jul 13. pii: JCO.2015.62.3488. [Epub ahead of print]
5. First Coast Service Options, Inc.  Local Coverage Determination (LCD):  G-CSF (Neupogen®, Granix™, Zarxio™) (L34002).  Centers for Medicare & Medicaid Services, Inc.  Updated on 10/12/2018 with effective date 10/01/2018.  Accessed March 2019.
6. Wisconsin Physicians Service Insurance Corporation. Local Coverage Determination (LCD): Human Granulocyte/Macrophage Colony Stimulating Factors (L34699).  Centers for Medicare & Medicaid Services, Inc.  Updated on 01/24/2019 with effective date 02/01/2019.  Accessed March 2019.
7. Palmetto GBA. Local Coverage Determination (LCD): White Cell Colony Stimulating Factors (L37176). Centers for Medicare & Medicaid Services, Inc.  Updated on 02/22/2019 with effective date 01/01/2019.  Accessed March 2019.
8. National Government Services, Inc. Local Coverage Article: Filgrastim, Pegfilgrastim, Tbo-filgrastim (e.g., Neupogen®, Neulasta™, Granix™, Zarxio™) - Related to LCD L33394 (A52408).  Centers for Medicare & Medicaid Services, Inc.  Updated on 12/28/2018 with effective date 01/01/2019.  Accessed March 2019.

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) 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/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

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