Coverage Policy Manual
Policy #: 2021024
Category: Pharmacy
Initiated: August 2021
Last Review: April 2024
  White Blood Cell Growth Factors (Colony Stimulating Factors)
Description:
Granulocyte colony-stimulating factor (G-CSF) and Granulocyte macrophage colony-stimulating factor (GM-CSF) are glycoproteins involved in the regulation and production of neutrophils.  Administration of exogenous G-CSF and GM-CSF results in the increase in total number of neutrophil counts, secondary to increased production of neutrophils (Clinical Pharmacology, 2017). This includes the following FDA approved products:
 
1. Long-acting pegfilgrastim agents (G-CSF):
a. Pegfilgrastim (e.g., Neulasta® and Neulasta OnPro®)
b. Pegfilgrastim-jmdb (e,g,. Fulphila®)
c. Pegfilgrastim-cbqv (e.g., Udenyca®)
d. Pegfilgrastim-bmez (e.g., Ziextenzo®)
e. Pegfilgrastim-apgf (e.g., Nyvepria®)
f. Pegfilgrastim-fpgk (e.g. Stimufend®)
g. Pegfilgrastim-pbbk (e.g., Fylnetra®)
h. Eflapegrastim-xnst (e.g., Rolvedon)
i. Elbemalenograstim alfa-vuxw (e.g., Ryzneuta)
j. Pegfigrastim-cbqv (e.g., Udenyca Onbody)
 
2. Short-acting filgrastim agents (G-CSF):
a. Filgrastim (e.g., Neupogen®)
b. Filgrastim-sndz (e.g., Zarxio®)
c. Filgrastim-aafi (e.g., Nivestym®)
d. Filgrastim-ayow (e.g., Reluko®)
e. Tbo-filgrastim (e.g., Granix®)
 
3. Sargramostim (e.g., Leukine®) (GM-CSF)
 
Regulatory Status
 
In 1991, the U.S. Food and Drug Administration (FDA) approved filgrastim (e.g. Neupogen).
In 1991, the FDA approved sargamostim (e.g., Leukine).
In 2002, the FDA approved pegfilgrastim (e.g. Neulasta). The subcutaneous delivery system (e.g., Neulasta Onpro kit with the On-body Injector) was approved in 2014.
In 2012, the FDA approved tbo-filgrastim (e.g., Granix).
In 2015, the FDA approved filgrastim-sndz (e.g., Zarxio).
In 2018, the FDA approved pegfilgrastim-jmdb (e.g. Fulphila).
In 2018, the FDA approved filgrastim-aafi (e.g. Nivestym).
In 2018, the FDA approved pegfilgrastim-cbqv (e.g., Udenyca).
In November 2019, the FDA approved pegfilgrastim-bmez (Ziextenzo).
In June 2020, the FDA approved pegfilgrastim-apgf (e.g. Nyvepria)
In February 2022, the FDA approved filgrastim (e.g. Releuko).
In May 2022, the FDA approved pegfilgrastim-pbbk (e.g., Fylnetra).
In September 2022, the FDA approved pegfilgrastim-fpgk (e.g. Stimufend).
In September 2022, the FDA approved eflapegrastim-xnst (e.g., Rolvedon).
In November 2023, the FDA approved, elbemalenograstim alfa-vuxw (e.g., Ryzneuta).
 
This policy applies to all drugs with granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor as the reference medication and have been designated by the FDA as a biosimilar.
 
Coding
 
See CPT/HCPCS Code section below.
 
Policy/
Coverage:
For members of plans that utilize a prescription drug program vendor (i.e., Arkansas State Employees and Public School Employees, Arkansas State Police and Arkansas State University) for preferred products under the medical benefit, the preferred products contained in this policy are NOT applicable. Please contact the member’s prescription drug program vendor.
 
Effective January 1, 2024, Prior Approval is required for White Blood Cell Growth Factors.
 
Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
 
Effective August 7, 2024
 
Select products (e.g., Zarxio, Nivestym, Nyvepria, Neulasta, and Neulasta OnPro) are preferred where there is an FDA approved indication for the biosimilar product and for all off-label uses of the reference product. According to the United States FDA “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.”
 
Preferred Products:
 
HCPCS                                  Brand Name                          Generic Name
J2506                                     Neulasta                                 Pegfilgrastim
J2506                                     Neulasta OnPro                       Pegfilgrastim
Q5101                                    Zarxio                                     Filgrastim-sndz
Q5110                                    Nivestym                                Filgrastim-aafi
Q5122                                    Nyvepria                                 Pegfilgrastim-apgf
 
Non-Preferred Products:
 
HCPCS                                  Brand Name                          Generic Name
J9361                                     Ryzneuta                                Efbemalenograstim alfa-vuxw
J1442                                     Neupogen                               Filgrastim
J2820                                     Leukine                                  Sargramostim   
Q5130                                    Fylnetra                                 Pegfilgrastim-pbbk
Q5127                                    Stimufend                              Pegfilgrastim-fpgk
J1449                                     Rolvedon                                Eflapegrastim-xnst
J1447                                     Granix                                   Tbo-filgrastim
Q5125                                    Releuko                                 Filgrastim-ayow     
Q5108                                    Fulphila                                 Pegfilgrastim-jmdb
Q5111                                    Udenyca                                Pegfilgrastim-cbqv
Q5111                                    Undenyca Onbody                  Pegfilgrastim-cbqv
Q5120                                    Ziextenzo                               Pegfilgrastim-bmez
 
If the request is for a non-preferred product, one of the following criteria must be met for the non-preferred product to be covered:
 
1. The individual has a documented serious adverse event to all preferred products that required medical intervention AND the prescriber has completed and submitted an FDA MedWatch Adverse Event Reporting Form for each event (the prescriber must provide a copy of the completed MedWatch form. Authorizations will not be considered unless the form is completed and submitted to the FDA); OR
2. None of the preferred products have an FDA-approved indication that is requested, and the requested non-preferred products has the FDA approved indication that is requested.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of granulocyte colony-stimulating factors (G-CSF) or granulocyte macrophage colony stimulating factors (GM-CSF) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following:  
 
PRIMARY PROPHYLAXIS OF FEBRILE NEUTROPENIA  (Any agent preferred)
Consideration should be given to equally effective and safe alternative chemotherapy treatment options that do not require CSF support, when available.
 
One white blood cell (WBC) growth factor agent is considered clinically appropriate for primary prophylaxis of chemotherapy-induced febrile neutropenia when ALL the following (1, 2, and 3) are met:  
 
1. The individual has a non-myeloid malignancy and is NOT receiving chemotherapy with radiation concurrently; AND
2. Chemotherapy intent must include one of the following:
a. Curative intent (adjuvant treatment for early-stage disease, for example); OR
b. Intent is survival prolongation, and the use of a different regimen or dose reduction would reduce the likelihood of reaching the treatment goal; OR
c. Intent is symptom management, and the use of a different regimen or dose reduction would reduce the likelihood of reaching the treatment goal.; AND
3. The individual falls into one of the following clinically significant risk categories for febrile neutropenia (FN) per AIM Specialty Health FN Risk Guideline: https://aimproviders.com/medoncology-arbcbs/resources/
a. High risk of febrile neutropenia (≥ 20%) based on chemotherapy regimen; OR
b. Intermediate risk of febrile neutropenia (≥ 10% but < 20%) based on chemotherapy regimen, and at least ONE of the following significant risk factors:
i. Age > 65 (Lyman 2014; Aagaard 2018)
ii. Poor performance status (ECOG 3 or 4, but chemotherapy still indicated) (Lyman 2014)
iii. Preexisting neutropenia, for example resulting from bone marrow damage or tumor infiltration (ANC < 1500 mm to the 3rd power) (Lyman 2014)
iv. Previous febrile neutropenia episode
v. Liver dysfunction, with bilirubin ≥ 1.0 or liver enzymes ≥ 2x upper limit of normal
vi. Presence of open wounds or active infections when chemotherapy cannot be delayed to accommodate recovery.
vii. Renal dysfunction with creatinine clearance of less than 50 mL/min (Lyman 2014) (Aagaard 2018)
viii. Poor nutritional status (baseline albumin less ≤ 3.5 g/dL or BMI less than 20)
ix. HIV infection (active) requiring ongoing antiviral therapy (Lyman 2014)
x. High tumor volume and/or high symptom burden from disseminated or unresectable malignancy
xi. Multiple serious comorbid conditions in addition to the treated malignancy
 
SECONDARY PROPHYLAXIS OF FEBRILE NEUTROPENIA (Any agent preferred)
Secondary prophylaxis of febrile neutropenia is considered clinically appropriate when there has been a previous neutropenic complication (in the absence of primary prophylaxis), and a change to the regimen (including dose reduction, schedule change, or change in therapy) would be expected to compromise individual outcome, particularly in the setting of curative intent. (NCCN 2A)
 
ADJUNCTIVE TREATMENT OF FEBRILE NEUTROPENIA (Any agent preferred)
Adjunctive treatment of febrile neutropenia is considered clinically appropriate when ANY of the following risk factors are present:
 
1. Age > 65
2. Neutrophil recovery is expected to be delayed (greater than 10 days)
3. Neutropenia is profound (< 0.1 x 10 to the 9th power)
4. Active pneumonia
5. Sepsis syndrome (hypotension and/or multi-organ damage/dysfunction noted)
6. Invasive fungal or opportunistic infection
7. Onset of fever during inpatient stay
 
Note: Febrile neutropenia (FN) is defined as an oral temperature > 38.3°C (101.0°F) or 2 consecutive readings of 38.0°C (100.4°F) for 1 hour, with an absolute neutrophil count less than 500 cells/microL (0.5 x 10 to the 9th power/L) or less than 1000 cells/microL and expected to fall below 500 cells/microL over the next 48 hours.
 
The use of multiple WBC growth factor agents for prophylaxis and/or adjunctive treatment within a given chemotherapy cycle is NOT clinically indicated.
 
OTHER ONCOLOGIC USES FOR WBC GROWTH FACTORS
The following indications by growth factor type are also considered clinically appropriate if the requirements below are met:
 
Filgrastim and biosimilars (G-CSF)
 
1. Acute lymphocytic leukemia (ALL):
a. After start of induction or first post-remission chemotherapy course; OR
b. As an alternate or adjunct to donor leukocyte infusions (DLI) for relapsed disease after transplant
2. Acute myeloid leukemia (AML)
a. After induction, reinduction, or consolidation; OR
b. As an alternate or adjunct to donor leukocyte infusions (DLI) for relapsed disease after transplant
3. Aplastic anemia, moderate or severe
4. Hairy cell leukemia (NCCN)
a. To treat severe neutropenia
5. Hematopoietic stem cell transplant (NCCN 2A)
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment; OR
c. To mobilize stem cells for collection by pheresis
6. Myelodysplastic syndrome (MDS) (NCCN 2A)
a. To treat recurrent infection; OR
b. To treat neutrophil count < 500 mm3; OR
c. MDS: Treatment of lower risk disease [(defined as IPSS-R (Very Low, Low, Intermediate), IPSS (Low/Intermediate-1), WPSS (Very Low, Low, Intermediate)] associated with symptomatic anemia, without del(5q), with or without other cytogenetic abnormalities, with serum erythropoietin ≤500 mU/mL and either of the following:
i. Ring sideroblasts ≥ 15% in combination with an erythropoiesis-stimulating agent (ESA); OR
ii. Ring sideroblasts < 15% in combination with lenalidomide and an ESA following no response (despite adequate iron stores) or loss of response to an ESA alone.
7. Radiation exposure
a. Following radiation therapy in the absence of chemotherapy if prolonged delays are expected; OR
b. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
8. Support for dose dense or dose intensive chemotherapy in any of the following scenarios:
a. Adjuvant treatment of high-risk breast cancer with combination therapy that includes anthracycline (doxorubicin or epirubicin)/cyclophosphamide followed by paclitaxel; OR
b. High-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer; OR
c. Chemotherapy intensification for newly diagnosed, localized Ewing sarcoma.
 
Pegfilgrastim and biosimilars (G-CSF)
 
1. Acute lymphocytic leukemia (ALL)
a. After start of induction or first post-remission chemotherapy course
2. Hematopoietic stem cell transplant
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment (NCCN 2A)
3. Myelodysplastic syndrome (MDS)
a. To treat recurrent infection; OR
b. To treat neutrophil count < 500 mm3
4. Radiation exposure
a. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
5. Support for dose dense chemotherapy in any of the following scenarios:
a. Adjuvant treatment of high-risk breast cancer with combination therapy that includes anthracycline (doxorubicin or epirubicin)/cyclophosphamide followed by paclitaxel; OR
b. High-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer; OR
c. Chemotherapy intensification for newly diagnosed localized Ewing sarcoma.
 
Sargramostim
 
1. Acute lymphocytic leukemia (ALL)
a. After start of induction or first post-remission chemotherapy course
2. Acute myeloid leukemia (AML)
a. After induction, reinduction, for individuals over 55 years of age
3. Hematopoietic stem cell transplant (NCCN 2A)
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment; OR
c. To mobilize stem cells for collection by pheresis
4. Myelodysplastic syndrome (MDS) (AHFS)
a. To treat recurrent infection; OR
b. To treat neutrophil count < 500 mm to the 3rd power
5. Radiation exposure
a. After radiation therapy in the absence of chemotherapy, if prolonged delays are expected; OR
b. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
6. Support for dose dense chemotherapy in any of the following scenarios:
a. Adjuvant treatment of high-risk breast cancer with combination therapy that includes anthracycline (doxorubicin or epirubicin)/cyclophosphamide followed by paclitaxel; OR
b. High-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer; OR
c. Chemotherapy intensification for newly diagnosed, localized Ewing sarcoma
7. In combination with naxitamab for pediatric individuals one year of age and older and adult individuals with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy.
 
Tbo-filgrastim
 
1. Hematopoietic stem cell transplant (NCCN 2A)
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment; OR
c. To mobilize stem cells for collection by pheresis
2. Myelodysplastic syndrome (NCCN 2A)
a. Treatment of lower risk disease [(defined as IPSS-R (Very Low, Low, Intermediate), IPSS (Low/Intermediate-1), WPSS (Very Low, Low, Intermediate)] associated with symptomatic anemia, without del(5q), with or without other cytogenetic abnormalities, with serum erythropoietin ≤ 500 mU/mL and either of the following:
i. Ring sideroblasts ≥15% in combination with an erythropoiesis-stimulating agent (ESA); OR
ii. Ring sideroblasts < 15% in combination with lenalidomide and an ESA following no response (despite adequate iron stores) or loss of response to an ESA alone
3. Radiation exposure
a. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
 
Dosing and Administration
Dosing per FDA Guidelines
 
Pegfilgrastim (e.g., Neulasta)
    • Individuals with cancer receiving myelosuppressive chemotherapy:
        • 6 mg administered subcutaneously once per chemotherapy cycle.
        • Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy.
        • Use weight-based dosing for pediatric individuals weighing less than 45 kg:
            • Weighing less than 10 kg = 0.1 mg/kg
            • Weighing 10-20 kg = 1.5 mg
            • Weighing 21-30 kg = 2.5 mg
            • Weighing 31-44 kg = 4 mg
    • Individuals acutely exposed to myelosuppressive doses of radiation:
        • Two doses, 6 mg each, administered subcutaneously one week apart. Administer the first dose as soon as possible after suspected or confirmed exposure to myelosuppressive doses of radiation, and a second dose one week after.
        • Use weight-based dosing for pediatric individuals weighing less than 45 kg:
            • Weighing less than 10 kg = 0.1 mg/kg
            • Weighing 10-20 kg = 1.5 mg
            • Weighing 21-30 kg = 2.5 mg
            • Weighing 31-44 kg = 4 mg
 
Pegfilgrastim-apgf (e.g., Nyvepria)
    • Individuals with cancer receiving myelosuppressive chemotherapy:
        • 6 mg administered subcutaneously once per chemotherapy cycle.
        • Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy.
        • Use weight-based dosing for pediatric individuals weighing less than 45 kg:
            • Weighing less than 10 kg = 0.1 mg/kg
            • Weighing 10-20 kg = 1.5 mg
            • Weighing 21-30 kg = 2.5 mg
            • Weighing 31-44 kg = 4 mg
 
Filgrastim-sndz (e.g., Zarxio) and Filgrastim-aafi (e.g., Nivestym)
    • Individuals with cancer receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML:
        • Recommended starting dose is 5 mcg/kg/day subcutaneous injection, short intravenous infusion (15 to 30 minutes), or continuous intravenous infusion.
    • Individuals with cancer undergoing bone marrow transplantation
        • 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours.
    • Individuals undergoing autologous peripheral blood progenitor cell collection and therapy:
        • 10 mcg/kg/day subcutaneous injection.
        • Administer for at least 4 days before first leukapheresis procedure and continue until last leukapheresis.
    • Individuals with congenital neutropenia:
        • Recommended starting dose is 6 mcg/kg subcutaneous injection twice daily.
    • Individuals with cyclic or idiopathic neutropenia:
        • Recommended starting dose is 5 mcg/kg subcutaneous injection daily.
    • Direct administration of less than 0.3 mL (180 mcg) is not recommended due to potential for dosing errors.
    • Filgrastim-sndz is available as 300 mcg/0.5 mL or 480 mcg/0.8 mL in a single-dose prefilled syringe.  
    • Filgrastim-aafi (e.g., Nivestym) is available as 300 mcg/mL or 480 mcg/1.6 mL (300 mcg/mL) in a single-dose vial and 300 mcg/0.5 mL or 480 mcg/0.8 mL in a single-dose prefilled syringe.  
 
Efbemalenograstim alfa-vuxw (e.g., Ryzneuta)
    • Recommended dose: 20 mg administered subcutaneously once per chemotherapy cycle.
    • Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy
    • Efbemalenograstim alfa-vuxw is available as 20 mg/mL solution in a single-dose prefilled syringe.
 
Sargramostim (e.g., Leukine)
    • AML, Neutrophil recovery following chemotherapy:
        • 250 mcg/square meters/day administered intravenously over a 4-hour period.
    • Mobilization of peripheral blood progenitor cells:
        • 250 mcg/square meters/day administered intravenously over 24 hours or subcutaneous injection once daily.
    • Post peripheral blood progenitor cell transplantation:
        • 250 mcg/square meters/day administered intravenously over 24 hours or subcutaneous injection once daily.
    • Myeloid reconstitution after autologous or allogeneic BMT:
        • 250 mcg/square meters/day administered intravenously over a 2-hour intravenous infusion.
    • Individuals acutely exposed to myelosuppressive doses of radiation, administer once daily as subcutaneous injection:
        • Adults and pediatric individuals weighing > 40 kg: 7 mcg/kg
        • Pediatric individual 15 kg to 40 kg: 10 mcg/kg
        • Pediatric individuals < 15 kg: 12 mcg/kg
    • Sargramostim is available as 250 mcg in single dose vial for reconstitution.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of granulocyte colony-stimulating factors (G-CSF) or granulocyte macrophage colony stimulating factors (GM-CSF), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of granulocyte colony-stimulating factors (G-CSF) or granulocyte macrophage colony stimulating factors (GM-CSF), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective May 15, 2024 to August 6, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Select products (e.g., Zarxio, Nivestym, Nyvepria, Neulasta, and Neulasta OnPro) are preferred where there is an FDA approved indication for the biosimilar product and for all off-label uses of the reference product. According to the United States FDA “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.”
 
Preferred Products:
 
HCPCS                                  Brand Name                          Generic Name
J2506                                     Neulasta                                 Pegfilgrastim
J2506                                     Neulasta OnPro                       Pegfilgrastim
Q5101                                    Zarxio                                     Filgrastim-sndz
Q5110                                    Nivestym                                Filgrastim-aafi
Q5122                                    Nyvepria                                 Pegfilgrastim-apgf
 
Non-Preferred Products:
 
HCPCS                                  Brand Name                          Generic Name
J9361                                     Ryzneuta                                Efbemalenograstim alfa-vuxw
J1442                                     Neupogen                               Filgrastim
J2820                                     Leukine                                  Sargramostim   
Q5130                                    Fylnetra                                 Pegfilgrastim-pbbk
Q5127                                    Stimufend                              Pegfilgrastim-fpgk
J1449                                     Rolvedon                                Eflapegrastim-xnst
J1447                                     Granix                                   Tbo-filgrastim
Q5125                                    Releuko                                 Filgrastim-ayow     
Q5108                                    Fulphila                                 Pegfilgrastim-jmdb
Q5111                                    Udenyca                                Pegfilgrastim-cbqv
Q5111                                    Undenyca Onbody                  Pegfilgrastim-cbqv
Q5120                                    Ziextenzo                               Pegfilgrastim-bmez
 
If the request is for a non-preferred product, one of the following criteria must be met for the non-preferred product to be covered:
 
1. The individual has a documented serious adverse event  to all preferred products that required medical intervention AND the prescriber has completed and submitted an FDA MedWatch Adverse Event Reporting Form for each event (the prescriber must provide a copy of the completed MedWatch form. Authorizations will not be considered unless the form is completed and submitted to the FDA); OR
2. None of the preferred products have an FDA-approved indication that is requested, and the requested non-preferred products has the FDA approved indication that is requested.
 
The use of granulocyte colony-stimulating factors (G-CSF) or granulocyte macrophage colony stimulating factors (GM-CSF) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following:  
 
PRIMARY PROPHYLAXIS OF FEBRILE NEUTROPENIA   (Any agent preferred)
Consideration should be given to equally effective and safe alternative chemotherapy treatment options that do not require CSF support, when available.
 
One white blood cell (WBC) growth factor agent is considered clinically appropriate for primary prophylaxis of chemotherapy-induced febrile neutropenia when ALL the following (1, 2, and 3) are met:  
 
1. The individual has a non-myeloid malignancy and is NOT receiving chemotherapy with radiation concurrently;
2. Chemotherapy intent must include one of the following:
a. Curative intent (adjuvant treatment for early-stage disease, for example); OR
b. Intent is survival prolongation, and the use of a different regimen or dose reduction would reduce the likelihood of reaching the treatment goal; OR
c. Intent is symptom management, and the use of a different regimen or dose reduction would reduce the likelihood of reaching the treatment goal.
3. The individual falls into one of the following clinically significant risk categories for febrile neutropenia (FN) per AIM Specialty Health FN Risk Guideline: https://aimproviders.com/medoncology-arbcbs/resources/
a. High risk of febrile neutropenia (≥ 20%) based on chemotherapy regimen; OR
b. Intermediate risk of febrile neutropenia (≥ 10% but < 20%) based on chemotherapy regimen, and at least ONE of the following significant risk factors:
i. Age > 65 (Lyman 2014; Aagaard 2018)
ii. Poor performance status (ECOG 3 or 4, but chemotherapy still indicated) (Lyman 2014)
iii. Preexisting neutropenia, for example resulting from bone marrow damage or tumor infiltration (ANC < 1500 mm to the 3rd power) (Lyman 2014)
iv. Previous febrile neutropenia episode
v. Liver dysfunction, with bilirubin ≥ 1.0 or liver enzymes ≥ 2x upper limit of normal
vi. Presence of open wounds or active infections when chemotherapy cannot be delayed to accommodate recovery.
vii. Renal dysfunction with creatinine clearance of less than 50 mL/min (Lyman 2014) (Aagaard 2018)
viii. Poor nutritional status (baseline albumin less ≤ 3.5 g/dL or BMI less than 20)
ix. HIV infection (active) requiring ongoing antiviral therapy (Lyman 2014)
x. High tumor volume and/or high symptom burden from disseminated or unresectable malignancy
xi. Multiple serious comorbid conditions in addition to the treated malignancy
 
SECONDARY PROPHYLAXIS OF FEBRILE NEUTROPENIA (Any agent preferred)
Secondary prophylaxis of febrile neutropenia is considered clinically appropriate when there has been a previous neutropenic complication (in the absence of primary prophylaxis), and a change to the regimen (including dose reduction, schedule change, or change in therapy) would be expected to compromise individual outcome, particularly in the setting of curative intent. (NCCN 2A)
 
ADJUNCTIVE TREATMENT OF FEBRILE NEUTROPENIA (Any agent preferred)
Adjunctive treatment of febrile neutropenia is considered clinically appropriate when ANY of the following risk factors are present:
 
1. Age > 65
2. Neutrophil recovery is expected to be delayed (greater than 10 days)
3. Neutropenia is profound (< 0.1 x 10 to the 9th power)
4. Active pneumonia
5. Sepsis syndrome (hypotension and/or multi-organ damage/dysfunction noted)
6. Invasive fungal or opportunistic infection
7. Onset of fever during inpatient stay
 
Note: Febrile neutropenia (FN) is defined as an oral temperature > 38.3°C (101.0°F) or 2 consecutive readings of 38.0°C (100.4°F) for 1 hour, with an absolute neutrophil count less than 500 cells/microL (0.5 x 10 to the 9th power/L) or less than 1000 cells/microL and expected to fall below 500 cells/microL over the next 48 hours.
 
The use of multiple WBC growth factor agents for prophylaxis and/or adjunctive treatment within a given chemotherapy cycle is NOT clinically indicated.
 
OTHER ONCOLOGIC USES FOR WBC GROWTH FACTORS
The following indications by growth factor type are also considered clinically appropriate if the requirements below are met:
 
Filgrastim and biosimilars (G-CSF)
 
1. Acute lymphocytic leukemia (ALL):
a. After start of induction or first post-remission chemotherapy course; OR
b. As an alternate or adjunct to donor leukocyte infusions (DLI) for relapsed disease after transplant
2. Acute myeloid leukemia (AML)
a. After induction, reinduction, or consolidation; OR
b. As an alternate or adjunct to donor leukocyte infusions (DLI) for relapsed disease after transplant
3. Aplastic anemia, moderate or severe
4. Hairy cell leukemia (NCCN)
a. To treat severe neutropenia
5. Hematopoietic stem cell transplant (NCCN 2A)
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment; OR
c. To mobilize stem cells for collection by pheresis
6. Myelodysplastic syndrome (MDS) (NCCN 2A)
a. To treat recurrent infection; OR
b. To treat neutrophil count < 500 mm3 OR
c. MDS: Treatment of lower risk disease [(defined as IPSS-R (Very Low, Low, Intermediate), IPSS (Low/Intermediate-1), WPSS (Very Low, Low, Intermediate)] associated with symptomatic anemia, without del(5q), with or without other cytogenetic abnormalities, with serum erythropoietin ≤500 mU/mL and either of the following:
i. Ring sideroblasts ≥ 15% in combination with an erythropoiesis-stimulating agent (ESA) OR
ii. Ring sideroblasts < 15% in combination with lenalidomide and an ESA following no response (despite adequate iron stores) or loss of response to an ESA alone.
7. Radiation exposure
a. Following radiation therapy in the absence of chemotherapy if prolonged delays are expected; OR
b. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
8. Support for dose dense or dose intensive chemotherapy in any of the following scenarios:
a. Adjuvant treatment of high-risk breast cancer with combination therapy that includes anthracycline (doxorubicin or epirubicin)/cyclophosphamide followed by paclitaxel; OR
b. High-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer;OR
c. Chemotherapy intensification for newly diagnosed, localized Ewing sarcoma.
 
Pegfilgrastim and biosimilars (G-CSF)
1. Acute lymphocytic leukemia (ALL)
a. After start of induction or first post-remission chemotherapy course
2. Hematopoietic stem cell transplant
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment (NCCN 2A)
3. Myelodysplastic syndrome (MDS)
a. To treat recurrent infection; OR
b. To treat neutrophil count < 500 mm3
4. Radiation exposure
a. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
5. Support for dose dense chemotherapy in any of the following scenarios:
a. Adjuvant treatment of high-risk breast cancer with combination therapy that includes anthracycline (doxorubicin or epirubicin)/cyclophosphamide followed by paclitaxel; OR
b. High-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer; OR
c. Chemotherapy intensification for newly diagnosed localized Ewing sarcoma.
 
Sargramostim
1. Acute lymphocytic leukemia (ALL)
a. After start of induction or first post-remission chemotherapy course
2. Acute myeloid leukemia (AML)
a. After induction, reinduction, for individuals over 55 years of age
3. Hematopoietic stem cell transplant (NCCN 2A)
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment; OR
c. To mobilize stem cells for collection by pheresis
4. Myelodysplastic syndrome (MDS) (AHFS)
a. To treat recurrent infection; OR
b. To treat neutrophil count < 500 mm to the 3rd power
5. Radiation exposure
a. After radiation therapy in the absence of chemotherapy, if prolonged delays are expected; OR
b. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
6. Support for dose dense chemotherapy in any of the following scenarios:
a. Adjuvant treatment of high-risk breast cancer with combination therapy that includes anthracycline (doxorubicin or epirubicin)/cyclophosphamide followed by paclitaxel; OR
b. High-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer; OR
c. Chemotherapy intensification for newly diagnosed, localized Ewing sarcoma
7. In combination with naxitamab for pediatric individuals one year of age and older and adult individuals with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy.
 
Tbo-filgrastim
1. Hematopoietic stem cell transplant (NCCN 2A)
a. To promote bone marrow myeloid recovery; OR
b. To treat delayed or failed engraftment; OR
c. To mobilize stem cells for collection by pheresis
2. Myelodysplastic syndrome (NCCN 2A)
a. Treatment of lower risk disease [(defined as IPSS-R (Very Low, Low, Intermediate), IPSS (Low/Intermediate-1), WPSS (Very Low, Low, Intermediate)] associated with symptomatic anemia, without del(5q), with or without other cytogenetic abnormalities, with serum erythropoietin ≤ 500 mU/mL and either of the following:
i. Ring sideroblasts ≥15% in combination with an erythropoiesis-stimulating agent (ESA) OR
ii. Ring sideroblasts < 15% in combination with lenalidomide and an ESA following no response (despite adequate iron stores) or loss of response to an ESA alone
3. Radiation exposure
a. After accidental or intentional body irradiation of doses greater than 2 Gy (hematopoietic syndrome of acute radiation syndrome) (NCCN 2A)
 
Dosing and Administration
Dosing per FDA Guidelines
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of granulocyte colony-stimulating factors (G-CSF) or granulocyte macrophage colony stimulating factors (GM-CSF), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of granulocyte colony-stimulating factors (G-CSF) or granulocyte macrophage colony stimulating factors (GM-CSF), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Due to the detail of the policy statement, the document containing the coverage statements for dates prior to Mary 15, 2024 are not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com
Rationale:
The American Society of Clinical Oncology  and the European Organisation for Research and Treatment of Cancer currently recommends primary prophylaxis with granulocyte-colony stimulating factors to reduce the incidence of febrile neutropenia when the chemotherapy regimen has an associated febrile neutropenia risk of 20%  or greater or the chemotherapy regimen has an associated risk of 10-20% and the patient has other risk factors that increase their likelihood of developing febrile neutropenia. Secondary prophylaxis is recommended if neutropenia has occurred in previous treatment cycle. (Aapro et al, 2011; Smith et al, 2015).
 
The  American Society of Clinical Oncology  and European Organisation for Research and Treatment of Cancer currently recommends G-CSF be administered to patients with current febrile neutropenia that are at a high risk of infection-related complications and have a poor prognosis based on factors that are predictive of poor clinical outcomes.   The routine use of G-CSF as treatment of uncomplicated febrile neutropenia is not recommended (Aapro et al, 2011).
 
The key points and recommendations from the ASCO 2015 practice guidelines update with regard to use of white blood cell growth factors is as follows (Smith et al, 2015):  
 
    • Primary prophylaxis with a CSF starting with the first cycle and continuing through subsequent cycles of chemotherapy is recommended in patients who have an approximately 20% or higher risk for febrile neutropenia based on patient-, disease- and treatment-related factors. Primary CSF prophylaxis should also be administered in patients receiving dose-dense chemotherapy when considered appropriate. Consideration should be given to alternative, equally effective, and safe chemotherapy regimens not requiring CSF support when available. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • Secondary prophylaxis with a CSF is recommended for patients who experienced a neutropenic complication from a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose or treatment delay may compromise disease-free or overall survival or treatment outcome. In many clinical situations, dose reduction or delay may be a reasonable alternative. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • CSFs should not be routinely used for patients with neutropenia who are afebrile. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • CSFs should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia. However, CSFs should be considered in patients with fever and neutropenia who are at high risk for infection-associated complications or who have prognostic factors predictive of poor clinical outcomes. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Efficacy data support the use of CSFs with dose-dense chemotherapy in the adjuvant treatment of high-risk breast cancer and with high–dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer. There are limited and conflicting data on the value of dose-dense regimens with CSF support in non-Hodgkin lymphoma (NHL), and this cannot routinely be recommended at this time. (Type: evidence based, benefits outweigh harms. Evidence quality: high for breast cancer and lymphoma; intermediate for urothelial cancer. Strength of recommendation: strong for breast cancer and lymphoma; moderate for urothelial cancer.)
    • CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral-blood progenitor cells. Choice of mobilization strategy depends in part on type of cancer and type of transplantation. (Type: evidence based, benefits outweigh harms. Evidence quality: strong. Strength of recommendation: high.)
    • CSFs should be administered after autologous stem-cell transplantation to reduce the duration of severe neutropenia. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • CSFs may be administered after allogeneic stem-cell transplantation to reduce the duration of severe neutropenia. (Type: evidence based. Evidence quality: low. Strength of recommendation: weak)
    • Prophylactic CSFs for patients with diffuse aggressive lymphoma age ൒65 years treated with curative chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) should be considered, particularly in the presence of comorbidities. (Type: evidence based, benefits outweigh harms. Evidence quality: intermediate. Strength of recommendation: moderate.)
    • The use of CSFs in pediatric patients will almost always be guided by clinical protocols. As in adults, the use of CSFs is reasonable as primary prophylaxis for pediatric patients with a high likelihood of febrile neutropenia. Similarly, the use of CSFs for secondary prophylaxis or for therapy should be limited to high-risk patients. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • For pediatric indications in which dose-intense chemotherapy is known to have a survival benefit, such as Ewing sarcoma, CSFs should be used to enable the administration of these regimens. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
    • CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection. (Type: informal consensus. Evidence quality: intermediate. Strength of recommendation: moderate.)
    • Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia. The choice of agent depends on convenience, cost, and clinical situation. There have been no additional data comparing granulocyte CSFs and granulocyte-macrophage CSFs since the 2006 update; therefore, there is no change in the recommendation regarding their therapeutic equivalency. (Type: evidence based, benefits outweigh harms. Evidence quality: high. Strength of recommendation: strong.)
 
Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, include the prompt administration of CSFs or pegylated granulocyte CSFs. (Type: formal consensus [by others], benefits outweigh harms. Evidence quality: intermediate. Strength of recommendation: moderate.)
 
In a randomized, double-blind, controlled study, biosimilar LA-EP2006 (Pegfilgrastim-bmez (Ziextenzo®), with reference pegfilgrastim in women receiving chemotherapy for breast cancer. Women were randomized to receive Ziextenzo or Neulasta. Results of this study showed LA-EP2006 was equivalent to reference. There were no clinically meaningful differences regarding efficacy and safety in breast cancer patients receiving chemotherapy. (Harbeck N, Lipatov O, Frolova M, et. al., 2016)
 
A multicenter, randomized, open-label study to evaluate the efficacy, safety, and pharmacokinetics of pegfilgrastim in pediatric and young adult patients with sarcoma was conducted. Patients with sarcoma receiving chemotherapy age 0 to 21 years were eligible. Patients were randomized to receive subcutaneous pegfilgrastim as a single-dose of 100 mcg/kg or subcutaneous filgrastim at a dose5 mcg/kg/day following myelosuppressive chemotherapy. Recovery of neutrophil counts was similar in the pegfilgrastim and filgrastim groups. (Spunt SL, Irving H, Frost J, et.al., 2010)
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2024. No new literature was identified that would prompt a change in the coverage statement.
 
CPT/HCPCS:
C9096Injection, filgrastim-ayow, biosimilar, (releuko), 1 microgram
J1442Injection, filgrastim (g csf), excludes biosimilars, 1 microgram
J1447Injection, tbo filgrastim, 1 microgram
J1449Injection, eflapegrastim-xnst, 0.1 mg
J2505Injection, pegfilgrastim, 6 mg
J2506Injection, pegfilgrastim, excludes biosimilar, 0.5 mg
J2820Injection, sargramostim (gm csf), 50 mcg
J3590Unclassified biologics
J9361Injection, efbemalenograstim alfa-vuxw, 0.5 mg
Q5101Injection, filgrastim sndz, biosimilar, (zarxio), 1 microgram
Q5108Injection, pegfilgrastim-jmdb (fulphila), biosimilar, 0.5 mg
Q5110Injection, filgrastim aafi, biosimilar, (nivestym), 1 microgram
Q5111Injection, pegfilgrastim-cbqv (udenyca), biosimilar, 0.5 mg
Q5120Injection, pegfilgrastim-bmez (ziextenzo), biosimilar, 0.5 mg
Q5122Injection, pegfilgrastim-apgf (nyvepria), biosimilar, 0.5 mg
Q5125Injection, filgrastim-ayow, biosimilar, (releuko), 1 microgram
Q5127Injection, pegfilgrastim-fpgk (stimufend), biosimilar, 0.5 mg
Q5130Injection, pegfilgrastim-pbbk (fylnetra), biosimilar, 0.5 mg
References: Aapro MS, Bohlius J, Cameron DA, et al.;(2011) European Organisation for Research and Treatment of Cancer.(2011) Eur J Cancer. 2011; 47(1):8-32.

AIM Medical Oncology:(2021) Clinical Appropriateness Guidelines for Febrile Neutropenia Risk, Clinical Appropriateness Guidelines for Febrile Neutropenia Risk,

AIM Medical Oncology:(2021) Clinical Appropriateness Guidelines for Febrile Neutropenia Risk, eff. July 2021.

Bennett CL, Djulbegovic B, Norris LB, et al.(2013) Colony-stimulating factors for febrile neutropenia during cancer therapy. N Engl J Med. 2013;368(12):1131-9. PMID: 23514290

Clinical Pharmacology.(2017) Pegfilgrastim. Tampa (FL): Elsevier. c2017- [cited 2017 January 18]. Available from: http://www.clinicalpharmacology.com

Cooper KL, Madan J, Whyte S, et al.(2011) Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer. 2011;11:404. PMID: 21943360

Crawford J, Armitage J, Balducci L, et al.(2013) Myeloid growth factors. J. 2013;11(10):1266-90. PMID: 24142827

Crawford J, Dale DC, Lyman GH.(2004) Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer. 2004;100(2):228-37. PMID: 14716755

Freyer G, Jovenin N, Yazbek G, et al.(2013) Granocyte-colony stimulating factor (G-CSF) has significant efficacy as secondary prophylaxis of chemotherapy-induced neutropenia in patients with solid tumors: results of a prospective study. Anticancer Res. 2013;33(1):301-7. PMID: 23267161

Fulphila® [package insert]. Mylan Pharmaceuticals, Inc.; Morgantown, WV (2020)

Fylnetra [package insert]. Piscataway, NJ. Kashiv BioSciences, LLC; Accessed at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761084s000lbl.pdf

Gilbar P, McPherson I, Sorour N, Sanmugarajah J.(2014) High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage. 2014;3:327-333.

Gilbar P, McPherson I, Sorour N, Sanmugarajah J.(2014) High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage. 2014;3:327-333.

Granix® [package insert]. Teva Pharmaceuticals USA, Inc.; North Wales, PA(2014)

Harbeck N, Lipatov O, Frolova M, et. al.(2016) Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer Future Oncol. 2016;12(11):1359–1367. doi:10.2217/fon-2016-0016

Hosmer W, Malin J, Wong M.(2011) Development and validation of a prediction model for the risk of developing febrile neutropenia in the first cycle of chemotherapy among elderly patients with breast, lung, colorectal, and prostate cancer. Support Care Cancer. 2011;19(3):333-41. PMID: 20179995

Hurvitz SA, Martin M, Symmans WF, et al.(2018) Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-126.

Hurvitz SA, Martin M, Symmans WF, et al.(2018) Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-126.

Leukine® [package insert]. Sanofi-aventis U.S. LLC.; Bridgewater, NJ(2013)

Lyman G, Abella E, and Pettengell R.(2014) Risk Factors for Febrile Neutropenia Among Patients With Cancer Receiving Chemotherapy: A Systematic Review. Crit Rev Oncol Hematol. 2014: 90 (3), 190-9.

Lyman G, Abella E, and Pettengell R.(2014) Risk Factors for Febrile Neutropenia Among Patients With Cancer Receiving Chemotherapy: A Systematic Review. Crit Rev Oncol Hematol. 2014: 90 (3), 190-9.

Lyman GH, Kuderer NM, Crawford J, et al.(2011) Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy. Cancer. 2011;117(9):1917-27. PMID: 21509769

Manko J, Walter-Croneck A, Jawniak D, et al.(2014) A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization. Pharmacol Rep. 2014;66(2):239-42. PMID: 24911076

Mhaskar R, Clark OA, Lyman G, et al.(2014) Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. [Review]

Mylan GmbH.Zurich,(2018) Fulphila [package insert]. Switzerland(2018)

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hematopoietic Growth Factors (Version 2.2020). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hematopoietic Growth Factors (Version 2.2020).

NCCN.(2017) Myeloid Growth Factors Version 1.2017. www.nccn.org/professionals/physician_gls/default.aspx

Neulasta® [package insert]. Amgen, Inc., Thousand Oaks, CA(2016)

Neupogen® [package insert]. Amgen, Inc., Thousand Oaks, CA(2015)

Nivestym® [package insert] Pfizer Inc; NY, NY(2018)

Nyvepria® [package insert] Pfizer Inc; NY, NY(2021)

Pfizer Inc; NY, NY(2021)(2005) Colony stimulating factors for prevention of myelosupressive therapy induced febrile neutropenia in children with acute lymphoblastic leukaemia. Cochrane Database Syst Rev. 2005(3):CD004139. PMID: 16034921

Releuko FDA Package Insert Accessed at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761082s000lbl.pdf

Schnipper LE, Smith TJ, Raghavan D, et al.(2012) American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. J Clin Oncol. 2012;30(14):1715-24. PMID: 22493340

Smith TJ, Khatcheressian J, Lyman GH, et al.(2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24(19):3187-205. PMID:16682719

Smith, T, et al;(2015) Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology 2015 33:28, 3199-3212

Spunt SL, Irving H, Frost J, et al.(2010) Phase II, randomized, open-label study of pegfilgrastim-supported VDC/IE chemotherapy in pediatric sarcoma patients. J Clin Oncol. 2010;28(8):1329–1336. doi:10.1200/JCO.2009.24.8872

Stimufend [package insert]. Lake Zurich, IL. Fresenius Kabi USA, LLC; Accessed at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761173Orig1s000correctedlbl.pdf

Udenyca® [package insert]. Coherus BioSciences, Inc.; Redwood City, CA (2021)

Womer RB, West DC, Krailo MD, et al.(2012) Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2012;30(33):4148-54. PMID: 23091096

Zarxio® [package insert]. Sandoz, Inc.; Princeton, NJ(2015)

Ziextenzo® [package insert]. Sandoz, Inc.; Princeton, NJ (2021)
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.