Granulocyte Colony Stimulating Factors – NC Standard

Restricted Product(s)

• Granix® (tbo-filgrastim) 
• Leukine® (sargramostim) 
• Neulasta® Neulasta OnPro® (pegfilgrastim) 
• Stimufend® (pegfilgrastim-fpgk) 
• Fylnetra® (pegfilgrastim-pbbk) 
• Neupogen® (filgrastim) 
• Nypozi™ (filgrastim-txid)
• Releuko™ (filfrastim-ayow) 
• Udenyca® Udenyca® ONBODY (pegfilgrastim-cbqv) 
• Ziextenzo™ (pegfilgrastim-bmez)

FDA Approved Use

• Neulasta®, Neulasta OnPro®, Udenyca®, Udenyca® ONBODY, Ziextenzo™, Fylnetra®, Stimufend® 
  • Indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 
  • Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome). 
  • Limitations of use: Not indicated for mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. 
• Granix® 
  • Indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. 
• Leukine® 
  • Use Following Induction Chemotherapy in Acute Myelogenous Leukemia: 
    • Indicated for use following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death. The safety and efficacy of Leukine have not been assessed in patients with AML under 55 years of age. 
    • The term acute myelogenous leukemia, also referred to as acute non-lymphocytic leukemia (ANLL), encompasses a heterogeneous group of leukemias arising from various non-lymphoid cell lines which have been defined morphologically by the French-American-British (FAB) system of classification. 
  • Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progentior Cells: indicated for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis. Mobilization allows for the collection of increased numbers of progenitor cells capable of engraftment as compared with collection without mobilization. After myeloablative chemotherapy, the transplantation of an increased number of progenitor cells can lead to more rapid engraftment, which may result in a decreased need for supportive care. Myeloid reconstitution is further accelerated by administration of Leukine following peripheral blood progenitor cell transplantation. 
  • Use in Myeloid Reconstitution After Autologous Bone Marrow Transplantation: indicated for acceleration of myeloid recovery in patients with non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin's disease undergoing autologous bone marrow transplantation (BMT). After autologous BMT in patients with NHL, ALL, or Hodgkin's disease, Leukine has been found to be safe and effective in accelerating myeloid engraftment, decreasing median duration of antibiotic administration, reducing the median duration of infectious episodes and shortening the median duration of hospitalization. Hematologic response to Leukine can be detected by complete blood count (CBC) with differential cell counts performed twice per week. 
  • Use in Myeloid Reconstitution After Allogeneic Bone Marrow Transplantation: indicated for acceleration of myeloid recovery in patients undergoing allogeneic BMT from HLA-matched related donors. Leukine has been found to be safe and effective in accelerating myeloid engraftment, reducing the incidence of bacteremia and other culture positive infections, and shortening the median duration of hospitalization. 
  • Use in Bone Marrow Transplantation Failure or Engraftment Delay: indicated in patients who have undergone allogeneic or autologous bone marrow transplantation (BMT) in whom engraftment is delayed or has failed. Leukine has been found to be safe and effective in prolonging survival of patients who are experiencing graft failure or engraftment delay, in the presence or absence of infection, following autologous or allogeneic BMT. Survival benefit may be relatively greater in those patients who demonstrate one or more of the following characteristics: autologous BMT failure or engraftment delay, no previous total body irradiation, malignancy other than leukemia or a multiple organ failure (MOF) score ≤ two (see CLINICAL EXPERIENCE). Hematologic response to Leukine can be detected by complete blood count (CBC) with differential performed twice per week. 
  • To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation. 
• Neupogen®,  Nypozi™, Releuko™ 
  • Patients with Cancer Receiving Myelosuppressive Chemotherapy: indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. 
  • Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). 
  • Patients with Cancer Undergoing Bone Marrow Transplantation: indicated to reduce the duration of neutropenia and neutropeniarelated clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. 
  • Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.
  • Patients with Severe Chronic Neutropenia: indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia. 
  • Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome): Neupogen is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation. 

Criteria for Approval of Restricted Product(s)

1. The request is for Neulasta, Neulasta OnPro, Udenyca, Udenyca ONBODY, Ziextenzo, Fylnetra, or Stimufend; AND 
   1. If the request is for Neulasta, Udenyca, Ziextenzo, Fylnetra, or Stimufend: 
      1. The patient has a documented serious adverse event that required medical intervention to both preferred pegfilgrastim biosimilar products Fulphila and Nyvepria that is not anticipated with the requested product; AND 
      2. The prescriber completed and submitted an FDA MedWatch Adverse Event Reporting Form (the prescriber must provide a copy of the completed MedWatch form. Authorization will not be considered unless the form is completed and submitted to the FDA); AND 
   2. If the request is for Neulasta OnPro or Udenyca ONBODY, the patient has an inability to physically or cognitively adhere to the treatment schedule including all of the following: 
      1. the inability to self-administer the medication; AND 
      2. lack of caregiver or support system for help with medication administration; AND 
   3. The medication will be used for Primary Prophylaxis for prevention of Febrile Neutropenia (FN); AND 
      1. The patient is on a chemotherapy regimen with an intermediate risk of FN (10-20%). In patients whose risk of developing febrile neutropenia is greater than or equal to 10% and less than 20% based on chemotherapy regimen, the use of primary prophylaxis should be reserved for those patients with one or more of the following risk factors for FN: 
         1. Age greater than 65 years; OR 
         2. Poor performance status; OR 
         3. Previous episodes of FN; OR 
         4. History of previous chemotherapy or radiation therapy; OR 
         5. After completion of combined chemoradiotherapy; OR 
         6. Bone marrow involvement by tumor producing cytopenias; OR 
         7. Preexisting neutropenia; OR 
         8. Poor nutritional status; OR
         9. Poor renal function; OR 
         10. Liver dysfunction (i.e., elevated bilirubin); OR 
         11. The presence of open wounds or active infections; OR 
         12. Recent surgery (generally within the past 12 weeks); OR 
         13. Advanced cancer; OR 
         14. Chronic immunosuppression in post-transplant including organ transplant; OR 
         15. Other serious comorbidities; OR
      2. The patient is on a chemotherapy regimen with a high risk of FN (>20%); OR 
      3. The patient is on chemotherapy regimen with an < 10% overall risk of FN; AND 
         1. The patient is at significant risk for serious medical consequences of FN, including death; AND 
         2. Chemotherapy is being used as a curative or adjuvant therapy; OR
   4. The medication will be used for Secondary Prophylaxis for prevention of FN: AND 
      1. The patient has had a previous neutropenic episode or dose-limiting event from a prior chemotherapy cycle and one following;
         1. The patient has history of colony stimulating factor use while on chemotherapeutic regimen; OR 
         2. The patient has no history of colony stimulating factor use; please see criteria for primary prophylaxis criteria; OR 
   5. The patient has been acutely exposed to myelosuppressive doses of radiation to increase survival; OR
2. The request is for Granix, Neupogen,  Nypozi, or Releuko; AND
   1. The patient had a documented life-threatening side effect that required medical intervention to both preferred filgrastim biosimilar products, Nivestym and Zarxio, that is not anticipated with the requested product; AND 
   2. The prescriber completed and submitted an FDA MedWatch Adverse Event Reporting Form (the prescriber must provide a copy of the completed MedWatch form. Authorization will not be considered unless the form is completed and submitted to the FDA); AND 
   3. The medication will be used for Primary Prophylaxis for prevention of Febrile Neutropenia (FN); AND 
      1. The patient is on a chemotherapy regimen with an intermediate risk of FN (10-20%). In patients whose risk of developing febrile neutropenia is greater than or equal to 10% and less than 20% based on chemotherapy regimen, the use of primary prophylaxis should be reserved for those patients with one or more of the following risk factors for FN: 
         1. Age greater than 65 years; OR 
         2. Poor performance status; OR 
         3. Previous episodes of FN; OR
         4. History of previous chemotherapy or radiation therapy; OR
         5. After completion of combined chemoradiotherapy; OR 
         6. Bone marrow involvement by tumor producing cytopenias; OR 
         7. Preexisting neutropenia; OR 
         8. Poor nutritional status; OR 
         9. Poor renal function; OR 
         10. Liver dysfunction (i.e., elevated bilirubin); OR 
         11. The presence of open wounds or active infections; OR 
         12. Recent surgery (generally within the past 12 weeks); OR 
         13. Advanced cancer; OR 
         14. Chronic immunosuppression in post-transplant including organ transplant; OR 
         15. Other serious comorbidities; OR
      2. The patient is on a chemotherapy regimen with a high risk of FN (>20%); OR 
      3. The patient is on chemotherapy regimen with an < 10% overall risk of FN; AND 
         1. The patient is at significant risk for serious medical consequences of FN, including death; AND 
         2. Chemotherapy is being used as a curative or adjuvant therapy; OR
   4. The medication will be used for Secondary Prophylaxis for prevention of FN; AND 
      1. The patient has had a previous neutropenic episode or dose-limiting event from a prior chemotherapy cycle and one of the following: 
         1. The patient has a history of colony stimulating factor use while on chemotherapeutic regimen; OR 
         2. The patient has no history of colony stimulating factor use; please see criteria for primary prophylaxis criteria; OR 
   5. The medication will be used for the Treatment of FN; AND 
      1. The patient has one of the following risk factors for the development of febrile neutropenia: 
         1. Sepsis syndrome; OR 
         2. Patient is greater than 65 years of age; OR 
         3. Absolute neutrophil count (ANC) <100 cells/mm3 ; OR 
         4. Prolonged neutropenia expected (>10 days); OR 
         5. Pneumonia or other clinically documented infections; OR 
         6. Invasive fungal infection; OR
         7. Hospitalization at the time of fever; OR 
         8. Prior episode of febrile neutropenia; OR
   6. The medication will be used for Severe Chronic Neutropenia: AND 
      1. The patient has at least one symptom (i.e. fever, infections, or ulcers); AND 
      2. Laboratory findings are consistent with severe chronic neutropenia (i.e. CBC with differential, platelet counts, and bone marrow morphology and karyotype); OR 
   7. The medication will be used for HIV/AIDS; AND 
      1. The patient’s absolute neutrophil count is ≤750 cells/ mm3 ; OR 
      2. The patient has drug-induced neutropenia (i.e. zidovudine, ganciclovir); OR 
   8. The medication will be used for Myelodysplastic Syndrome; AND 
      1. The patient has a history of recurrent or resistant infections with an ANC ≤500 cells/ mm3 ; OR 
      2. Increasing erythropoietic activity for the treatment of refractory anemia; AND 
         1. The patient is concurrently on an erythropoietic agent (Epogen, Procrit); AND 
         2. Serum erythropoietin level ≤500 mU/mL; AND 
         3. Adequate iron stores with ≥20% transferrin saturation or serum ferritin ≥100 ng/ml; OR 
   9. The patient has been diagnosed with Acute Myeloid Leukemia (AML); AND 
      1. The patient is receiving induction or consolidation chemotherapy (for improvement of fever duration and time for neutrophil recovery); OR 
   10. The patient has been diagnosed with a Non-myeloid Malignancy; AND 
       1. The patient is undergoing myeloablative chemotherapy followed by autologous or allogeneic bone marrow transplantation (BMT); OR 
   11. The patient has been diagnosed with aplastic anemia; OR 
   12. The medication will be used for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; OR 
   13. The patient has been acutely exposed to myelosuppressive doses of radiation to increase survival; OR
3. The request is for Leukine; AND 
   1. The medication will be used for Primary Prophylaxis for prevention of Febrile Neutropenia (FN); AND
      1. The patient is on a chemotherapy regimen with an intermediate risk of FN (10-20%). In patients whose risk of developing febrile neutropenia is greater than or equal to 10% and less than 20% based on chemotherapy regimen, the use of primary prophylaxis should be reserved for those patients with one or more of the following risk factors for FN:
         1. Age greater than 65 years; OR 
         2. Poor performance status; OR 
         3. Previous episodes of FN; OR 
         4. History of previous chemotherapy or radiation therapy; OR 
         5. After completion of combined chemoradiotherapy; OR 
         6. Bone marrow involvement by tumor producing cytopenias; OR 
         7. Preexisting neutropenia; OR 
         8. Poor nutritional status; OR 
         9. Poor renal function; OR 
         10. Liver dysfunction (i.e., elevated bilirubin); OR 
         11. The presence of open wounds or active infections; OR 
         12. Recent surgery (generally within the past 12 weeks); OR 
         13. Advanced cancer; OR 
         14. Chronic immunosuppression in post-transplant including organ transplant; OR 
         15. Other serious comorbidities; OR 
      2. The patient is on a chemotherapy regimen with a high risk of FN (>20%); OR 
      3. The patient is on chemotherapy regimen with an < 10% overall risk of FN; AND
         1. The patient is at significant risk for serious medical consequences of FN, including death; AND 
         2. Chemotherapy is being used as a curative or adjuvant therapy; OR
   2. The medication will be used for Secondary Prophylaxis for prevention of FN; AND 
      1. The patient has had a previous neutropenic episode or dose-limiting event from a prior chemotherapy cycle and one following:
         1. The patient has history of colony stimulating factor use while on chemotherapeutic regimen; OR 
         2. The patient has no history of colony stimulating factor use; please see criteria for primary prophylaxis criteria; please see criteria for primary prophylaxis criteria; OR 
   3. The medication will be used for the Treatment of FN; AND
      1. The patient has one of the follow risk factors for the development of febrile neutropenia 
         1. Sepsis syndrome; OR 
         2. Patient is greater than 65 years of age; OR 
         3. Absolute neutrophil count (ANC) <100 cells/mm3 ; OR 
         4. Prolonged neutropenia expected (>10days) ; OR 
         5. Pneumonia or other clinically documented infections; OR 
         6. Invasive fungal infection; OR 
         7. Hospitalization at the time of fever; OR 
         8. Prior episode of febrile neutropenia; OR
   4. The medication will be used for Severe Chronic Neutropenia; AND 
      1. The patient has at least one symptom (i.e. fever, infections, or ulcers); AND 
      2. Laboratory findings are consistent with severe chronic neutropenia (i.e. CBC with differential, platelet counts, and bone marrow morphology and karyotype); OR 
   5. The medication will be used for HIV/AIDS; AND 
      1. The patient’s absolute neutrophil count is ≤750 cells/ mm3 ; OR 
      2. The patient has drug-induced neutropenia (i.e. zidovudine, ganciclovir); OR 
   6. The medication will be used for Myelodysplastic Syndrome; AND 
      1. The patient has a history of recurrent or resistant infections with an ANC ≤500 cells/ mm3 ; OR 
      2. Increasing erythropoietic activity for the treatment of refractory anemia; AND 
         1. The patient is concurrently on an erythropoietic agent (Epogen, Procrit); AND 
         2. Serum erythropoietin level ≤500 mU/mL; AND 
         3. Adequate iron stores with ≥20% transferrin saturation or serum ferritin ≥100 ng/ml; OR 
   7. The patient has been diagnosed with Acute Myeloid Leukemia (AML); AND 
      1. The patient is receiving induction or consolidation chemotherapy (for improvement of fever duration and time for neutrophil recovery); OR 
   8. The patient has been diagnosed with a Non-myeloid Malignancy; AND 
      1. The patient is undergoing myeloablative chemotherapy followed by autologous or allogeneic bone marrow transplantation (BMT); OR 
   9. The patient has been diagnosed with aplastic anemia; OR
   10. The medication will be used for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; OR 
   11. The patient has undergone an allogeneic or autologous BMT and has a delayed or failed engraftment; OR 
   12. The patient has been diagnosed with malignant melanoma; OR 
   13. The patient has been diagnosed with radiation exposure; AND 
       1. The patient received radiation therapy in the absence of chemotherapy; AND 
       2. The patient experienced prolonged delays in treatment secondary to neutropenia; OR 
       3. The patient was irradiated with doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome); AND
4. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.
   
   Duration of Approval: 24 weeks

References

All information referenced is from FDA package insert unless otherwise noted below.

Policy Implementation/Update Information

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

December 2024: Criteria update: Added new to market product Nypozi (filgrastim-txid) with requirement of trial and failure of both Nivestym and Zarxio.
April 2024: Criteria change: Fulphila and Nyvepria preferred over Udenyca and Ziextenzo. Added Limitations of use for Neulasta, Neulasta OnPro, Udenyca, Udenyca ONBODY, Ziextenzo, Fylnetra, Stimufend. Added P&T review statement.
December 2022: Criteria update: Added new to market Stimufend to the criteria.
October 2022: Criteria update: Added new to market Fylnetra to the criteria.
June 2022: Criteria update: Removed preferred products from policy: Nivestym, Udenyca, Zarvio, and Ziextenzo.
March 2022: Criteria update: Added new to market Releuko to the criteria.
February 2022: Criteria update: Updated primary prophylaxis risk factors to include chronic immunosuppression in post-transplant
August 2021: Criteria change: Udenyca and Ziextenzo preferred over Fulphila and Nyvepria. Zarvio and Nivestym preferred over Granix and Neupogen.
January 2021: Criteria change: Policy changed to apply to Net Results. Biosimilar products preferred over Neulasta and Neupogen.
July 2020: Criteria change: For Neulasta and Neupogen requests, added requirement of a documented life-threatening side effect that required medical intervention to a biosimilar pegfilgrastim/filgrastim product and a submitted MedWatch Adverse Event Reporting form.
March 2020: Criteria change: Removed requirement of inadequate access to a healthcare facility for help with medication administration for requests for Neulasta OnPro.
November 2019: Criteria update: Added new to market Ziextenzo to policy.
January 2019: Added step therapy through biosimiliars for Neulasta and Neupogen; added Neulasta OnPro to the policy.
December 2018: Added new to market Udenyca to the criteria.
September 2018: new to market Nivestym added to criteria.
July 2018: Policy format updated; new to market Fulphila added to criteria at parity with Neulasta; Radiation exposure indication added for Leukine.
Jan 2017: Original utilization management criteria issued.