Highmark Commercial Medical Policy - Pennsylvania


 
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Medical Policy: I-88-011
Topic: Granulocyte Colony-Stimulating Factors
Section: Injections
Effective Date: August 20, 2018
Issue Date: August 20, 2018
Last Reviewed: July 2018

The class of drugs known as granulocyte colony stimulating factors (G-CSFs) include: Filgrastim (Neupogen®), Filgrastim-sndz, (Zarxio®), Pegfilgrastim (Neulasta®) (Neulasta® Onpro®), Pegfilgrastim-jmdb (Fulphila™), Tbo-filgrastim (Granix®) and Sargramostim (Leukine®). These drugs are used for the prevention of severe neutropenia, reduce the duration of the neutropenia, prevent febrile neutropenia (FN), and possible infection-related complications in individuals with cancer. FN is defined as a single temperature equal to or greater than 38.3°C, or a temperature equal to or greater than 38.0°C over 1 hour, and neutrophils less than 500 mcL.

G-CSFs are a blood growth factor that stimulates the bone marrow to produce more infection-fighting white blood cells known as neutrophils. These neutrophils are then released into the blood stream where they aid in fighting infection. When neutrophil levels drop and an individual becomes neutropenic, the body is less able to fight off infection. Individuals at high risk to develop these types of conditions may be clinically indicated for the administration of G-CSFs.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Note: Risk assessment for use of G-CSFs includes (not an all-inclusive list) disease type, chemotherapy regimen (high-dose, dose-dense, or standard-dose), risk factors, and treatment intent (curative/adjuvant vs. palliative). Independent clinical judgment should be exercised based on the individual’s situation.

Filgrastim (Neupogen®) may be considered medically necessary for ANY of the following indications:

FDA Indications:

  • Individuals with nonmyeloid malignancies receiving myelosuppressive anticancer drug therapy associated with significant incidence of severe neutropenia with fever to decrease incidence of infection; or
  • Individuals with acute myeloid leukemia (AML) following induction or consolidation chemotherapy to reduce the time to neutrophil recovery and duration of fever; or
  • Individuals with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) to reduce duration of neutropenia and neutropenia-related clinical sequalae; or
  • Individuals undergoing autologous peripheral blood progenitor cell collection and therapy for mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis; or
  • For chronic administration in individuals with severe chronic neutropenia to reduce incidence and duration of sequelae of neutropenia in symptomatic individuals with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia; or
  • Individuals acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) to increase survival.

NCCN Indications:

  • Myelodysplastic Syndromes (MDS):
    • Treatment of lower risk* disease associated with symptomatic anemia, without del(5q) with or without other cytogenetic abnormalities, with serum erythropoietin levels less than or equal to 500 mU/mL, and ring sideroblasts greater than or equal to 15%:
      • In combination with epoetin alfa or darbepoetin alfa; or
      • In combination with lenalidomide and epoetin alfa, or lenalidomide and darbepoetin alfa if no response to hematopoietic cytokines alone; or
    • Treatment of lower risk* disease associated with symptomatic anemia in combination with epoetin alfa or darbepoetin alfa, without del(5q), with or without cytogenetic abnormalities, with serum erythropoietin levels less than or equal to 500 mU/mL, ring sideroblasts less than 15%, and no response to epoetin alfa or darbepoetin alfa alone.
  • Myeloid Growth Factors:
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in high-risk (greater than 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings; or
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in intermediate-risk (10% to 20% overall risk of FN) individuals  with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings who have one (1) or more of the following risk factors (see Table 1):
      • Prior chemotherapy or radiation therapy
      • Persistent neutropenia
      • Bone marrow involvement by tumor
      • Recent surgery and/or open wounds
      • Liver dysfunction (bilirubin greater than 2.0)
      • Renal dysfunction (CrCl less than 50 mL/min)
      • Age greater than 65 years receiving full chemotherapy dose intensity; or
    • As treatment of chemotherapy-induced FN in individuals who:
      • Have been receiving prophylactic filgrastim; or
      • Have not received prophylactic granulocyte colony-stimulating factors but who have one or more risk factors for an infection-associated complication (see Table 2):
        • Sepsis syndrome
        • Age greater than 65 years
        • 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; or
    • Used in hematopoietic cell transplant for:
      • Mobilization of hematopoietic progenitor cells in the autologous setting as a single agent, following combination chemotherapy, or in combination with sargramostim; or
      • Mobilization of hematopoietic progenitor cells in combination with plerixafor in the autologous setting for individuals with non-Hodgkin lymphoma or multiple myeloma; or
      • Mobilization of donor hematopoietic progenitor cells (preferred**) or for granulocyte transfusion in the allogeneic setting; or
      • As supportive care in the post-transplant setting.
  • Acute Myeloid Leukemia (AML)
    • As treatment induction in individuals less than 60 years in age in combination with fludarabine, high-dose cytarabine, and idarubicin; or
    • As a component of repeating the initial successful induction regimen if late relapse (greater than or equal to 12 months); or
    • For relapsed or refractory disease in combination with ONE of the following:
      • Cladribine and cytarabine, with or without mitoxantrone or idarubicin: or
      • Fludarabine and cytarabine, with or without idarubicin; or
      • Clofarabine and cytarabine, with or without idarubicin
Procedure Codes
J1442



Note: Filgrastim (Neupogen), J1442, excludes biosimilar reference in its definition and should therefore be reported with code Q5101 to report the biosimilarity of filgrastim.                                     



Filgrastim-sndz (Zarxio) may be considered medically necessary for ANY of the following indications:

FDA Indications

  • Individuals with nonmyeloid malignancies receiving myelosuppressive anticancer drug therapy associated with significant incidence of severe neutropenia with fever to decrease incidence of infection; or
  • Individuals with AML following induction or consolidation chemotherapy to reduce the time to neutrophil recovery and duration of fever following treatments; or
  • Individuals with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT to reduce duration of neutropenia and neutropenia-related clinical sequalae; or
  • Individuals undergoing autologous peripheral blood progenitor cell collection and therapy for mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis; or
  • For chronic administration in individuals with severe chronic neutropenia to reduce incidence and duration of sequelae of neutropenia in symptomatic individuals with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

NCCN Indications:

  • MDS:
    • Treatment of lower risk* disease associated with symptomatic anemia, without del(5q), with or without other cytogenetic abnormalities, with serum erythropoietin levels less than or equal to 500 mU/mL, and ring sideroblasts greater than or equal to 15%:
      • In combination with epoetin alfa or darbepoetin alfa; or
      • In combination with lenalidomide and epoetin alfa, or lenalidomide and darbepoetin alfa following no response to hematopoietic cytokines alone; or
  • For treatment of lower risk* disease associated with symptomatic anemia in combination with epoetin alfa or darbepoetin alfa, without del(5q), with or without other cytogenetic abnormalities, serum erythropoietin levels less than or equal to 500 mU/mL, ring sideroblasts less than 15%, and no response to epoetin alfa or darbepoetin alfa alone.
    Myeloid Growth Factors:
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in high-risk (greater than 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings;or
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in intermediate-risk (10% to 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings who have one or more of the following risk factors (see Table 1):
      • Prior chemotherapy or radiation therapy
      • Persistent neutropenia
      • Bone marrow involvement by tumor
      • Recent surgery and/or open wounds
      • Liver dysfunction (bilirubin greater than 2.0)
      • Renal dysfunction (CrCl less than 50 mL/min)
      • Age greater than 65 years receiving full chemotherapy dose intensity;or
    • As treatment of chemotherapy-induced FN in individuals who:
      • Have been receiving prophylactic filgrastim-sndz; or
      • Have not received prophylactic G-CSFs but who have one or more risk factors for an infection-associated complication (see Table 2):
        • Sepsis syndrome
        • Age greater than 65 years
        • 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; or
    • Used in hematopoietic cell transplant for:
      • Mobilization of hematopoietic progenitor cells in the autologous setting as a single agent, following combination chemotherapy, or in combination with sargramostim; or
      • For mobilization of donor hematopoietic progenitor cells in combination with plerixafor in the autologous setting for individuals with non-Hodgkin lymphoma or multiple myeloma; or
      • Mobilization of donor hematopoietic progenitor cells or for granulocyte transfusion in the allogenic setting; or
      • As supportive care in the post-transplant setting.
Procedure Codes
Q5101



Note: Filgrastim (Neupogen), J1442, excludes biosimilar reference in its definition and should therefore be reported with code Q5101 to report the biosimilarity of filgrastim.                                     



Filgrastim-aafi (Nivestym™) may be considered medically necessary for ANY of the following:

FDA Indications:

  • Individuals with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with clinically significant incidence of FN to decrease the incidence of infection; or
  • Individuals with AML following induction or consolidation chemotherapy to reduce the time to neutrophil recovery and duration of fever following treatments; or
  • Individuals with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT to reduce duration of neutropenia and neutropenia-related clinical sequalae; or
  • Individuals undergoing autologous peripheral blood progenitor cell collection and therapy for mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis; or
  • Reduce the incidence and duration of sequealae of severe neutropenia in symptomatic individuals with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.
Procedure Codes
J3490



Pegfilgrastim  (Neulasta®) and (Neulasta® Onpro®) may be considered medically necessary for ANY of the following:

FDA Indications:

  • Individuals with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of FN to decrease the incidence of infection; or
  • Individuals acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) to increase survival.

NCCN Indications:

  • Myeloid Growth Factors:
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in high-risk (greater than 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings; or
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in intermediate-risk (10% to 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings who have one (1) or more of the following risk factors (see Table 1):
      • Prior chemotherapy or radiation therapy
      • Persistent neutropenia
      • Bone marrow involvement by tumor
      • Recent surgery and/or open wounds
      • Liver dysfunction (bilirubin greater than 2.0)
      • Renal dysfunction (CrCl less than 50 mL/min)
      • Age greater than 65 years receiving full chemotherapy dose intensity;or
    • Used for supportive care in the post autologous hematopoietic cell transplant setting.
Procedure Codes
J2505, 96377



Pegfilgrastim-jmdb  (Fulphila™) may be considered medically necessary for the following:

FDA Indication:

  • Individuals with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of FN to decrease the incidence of infection.
Procedure Codes
J3490



Note: Pegfilgrastim-jmdb (Fulphila) is not indicated for the mobilization or peripheral blood progenitor cells for hematopoietic stem cell transplantation.



Tbo-filgrastim (Granix) may be considered medically necessary for ANY of the following:

FDA Indication:

  • To reduce the duration of severe neutropenia in individuals with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of FN.

NCCN Indications:

  • MDS:
    • Treatment of lower risk* disease associated with symptomatic anemia, without del(5q) with or without other cytogenetic abnormalities, serum erythropoietin levels less than or equal to 500 mU/mL, and ring sideroblasts greater than or equal to 15%:
      • In combination with epoetin alfa or darbepoetin alfa; or
      • In combination with lenalidomide and epoetin alfa, or lenalidomide and darbepoetin alfa if no response to hematopoietic cytokines alone; or
    • Consider in combination with epoetin alfa or darbepoetin alfa for lower risk* disease associated with symptomatic anemia, without del(5q), with or without cytogenetic abnormalities, with serum erythropoietin levels less than or equal to 500 mU/mL, ring sideroblasts less than 15%, and no response to epoetin alfa or darbepoetin alfa alone.

  • Myeloid Growth Factors:
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in high-risk (greater than 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings;or
    • Prophylaxis of chemotherapy-induced FN or other dose-limiting neutropenic events in intermediate-risk (10% to 20% overall risk of FN) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings who have one (1) or more of the following risk factors (see Table 1):
      • Prior chemotherapy or radiation therapy
      • Persistent neutropenia
      • Bone marrow involvement by tumor
      • Recent surgery and/or open wounds
      • Liver dysfunction (bilirubin greater than 2.0)
      • Renal dysfunction (CrCl less than 50 mL/min)
      • Age greater than 65 years receiving full chemotherapy dose intensity; or
    • Treatment of chemotherapy-induced FN in individuals who have been receiving prophylactic tbo-filgrastim; or
    • Used in hematopoietic cell transplant for:
      • Mobilization of hematopoietic progenitor cells in the autologous setting as a single agent, following combination chemotherapy; or
      • Mobilization of hematopoietic progenitor cells in combination with plerixafor in the autologous setting for individuals with non-Hodgkin lymphoma or multiple myeloma; or
      • Mobilization of donor hematopoietic progenitor cells or for granulocyte transfusion in the allogeneic setting; or
      • Supportive care in the post-transplant setting.
Procedure Codes
J1447



Sargramostim (Leukine) may be considered medically necessary for ANY of the following indications:

FDA Indications:

  • Individuals 55 years and older with AML following induction chemotherapy to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death; or
  • Adult individuals undergoing mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation; or
  • Individuals 2 years of age or older for the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation; or
  • Individuals 2 years or age or older for the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation; or
  • Individuals 2 years or age or older for treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation; or
  • Individuals acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) to increase survival.

NCCN Indications

  • Myeloid Growth Factors:
    • Treatment of chemotherapy-induced FN in individuals who have not received prophylactic G-CSFs but who have one or more risk factors for an infection-associated complication (see Table 2):
      • Sepsis syndrome
      • Age greater than 65 years
      • 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; or
    • Used in hematopoietic cell transplant for the mobilization of hematopoietic progenitor cells in combination with filgrastim or filgrastim-sndz in the autologous setting.

The safety and efficacy of sargramostim have not been assessed in individuals with AML less than 55 years of age.

Liquid solutions containing benzyl alcohol (including liquid sargramostim or lyophilized Leukine reconstituted with bacteriostatic water for injection, USP (0.9% benzyl alcohol)) should not be administered to neonates.

Procedure Codes
J2820



The use of G-CSFs (filgrastim, filgrastim-sndz, filgrastim-aafi, pegfilgrastim, pegfilgrastim-jmdb, tbo-filgrastim and sargramostim) are considered not medically necessary for ANY of the following:

  • For uses not meeting the criteria above; or
  • As prophylaxis for FN, except when criteria above are met; or
  • As treatment of neutropenia in individuals who are afebrile, except when criteria above are met; or
  • As adjunctive therapy in individuals with uncomplicated FN, defined as: fever less than ten (10) days duration, no evidence of pneumonia, cellulitis, abscess, sinusitis, hypotension, multi-organ dysfunction, or invasive fungal infection; and no uncontrolled malignancies; or
  • Chemo sensitization of myeloid leukemias; or
  • As prophylaxis for FN during concomitant chemotherapy and radiation therapy; or
  • Continued use if no response is seen within 28-42 days (individuals who have failed to respond within this time frame are considered non-responders).
Procedure Codes
J1442, J1447, J2505, J2820, Q5101, J3490



Note: Dosage recommendations per the FDA label.

*Note: Lower risk defined as IPSS-R (Very Low, Low, Intermediate), IPSS (Low/Intermediate-1), and WPSS (Very Low, Low, Intermediate).

**Note: Language derived from National Comprehensive Cancer Network (NCCN) guidelines.

 



Place of Service: Outpatient

The administration of G-CSFs is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.


The policy position applies to all commercial lines of business


Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

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Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
    • Qualified sign language interpreters
    • Written information in other formats (large print, audio, accessible electronic formats, other formats)
  • Provides free language services to people whose primary language is not English, such as:
    • Qualified interpreters
    • Information written in other languages
If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.



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