DESCRIPTION
Colony stimulating factors (CSFs) are naturally occurring cytokine glycoproteins classified as immunomodulators. They serve as growth factors specifically for myeloid hematopoietic cells. One type of CSF, granulocyte colony stimulating factor (G-CSF), modulates neutrophils and their precursors, regulating their production within the bone marrow and affecting neutrophil progenitor proliferation, differentiation and selected end-cell functional activation (e.g., enhanced phagocytic ability, antibody dependent killing). Some G-CSFs have been reproduced by recombinant DNA technology for clinical use (rG-CSFs).
Examples of G-CSFs are filgrastim (Neupogen®) and pegfilgrastim (Neulasta®).
REFER TO DECISION SUPPORT TREE
POLICY
Filgrastim
Filgrastim for use by individuals receiving anti-cancer treatment is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Filgrastim for the mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis is medically necessary.
Filgrastim for the treatment of neutropenia is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Filgrastim to accelerate myeloid recovery is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Filgrastim to prolong survival in bone marrow transplantation (BMT) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Filgrastim for the treatment of acquired immunodeficiency syndrome (AIDS) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Filgrastim for the treatment of other conditions/diseases, including, but not limited to, the following is considered investigational: (See Applicable Tennessee State Mandate Requirements listed below.)
Enhancement of the efficacy of myelosuppressive chemotherapy
To shorten the duration of chemotherapy
Prophylactic treatment
Adjunction to empiric anti-infective therapy with the development of febrile neutropenia secondary to chemotherapy-induced myelosuppression
To prevent subsequent episodes of febrile neutropenia secondary to chemotherapy induced myelosuppression
Treatment of hairy cell leukemia
Pegfilgrastim
Pegfilgrastim to decrease the incidence of infection is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Pegfilgrastim for the treatment of other conditions/diseases, including, but not limited to, the following is considered investigational:
Use in individuals receiving antimetabolites such as 5-fluorouracil
Use in individuals receiving antineoplastic agents that are associated with delayed myelosuppression (e.g., nitrosoureas, mitomycin C)
Use in individuals receiving radiation therapy
Policies with similar titles: Granulocyte-Macrophage Colony Stimulating Factors (GM-CSF)
MEDICAL APPROPRIATENESS
Filgrastim
Filgrastim for use by individuals receiving anti-cancer treatment is considered medically appropriate if ANY ONE of the following criteria are met:
The individual has a non-myeloid malignancy and has ALL of the following:
Increased incidence of infection as manifested by febrile neutropenia
Is receiving myelosuppressive chemotherapeutic agents associated with a significant incidence of severe neutropenia (absolute neutrophil count less than 500/mm3) with fever (e.g., doxorubicin, docetaxel)
The individual has acute myelocytic leukemia and has undergone ANY ONE of the following:
Induction chemotherapy
Consolidation chemotherapy
The individual is to receive bone marrow transplantation (BMT) with ALL of the following:
A non-myeloid malignancy
Is undergoing myeloablative chemotherapy
Filgrastim for the treatment of neutropenia is considered medically appropriate if ANY ONE of the following criteria are met:
The individual has severe chronic neutropenia (congenital, cyclic or idiopathic) with ALL of the following:
An absolute neutrophil count (ANC) of less than 500/mm3
Increased incidence and duration of clinical sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers)
The individual has drug-induced neutropenia
The individual has neutropenia associated with bone marrow transplantation (BMT)
Filgrastim to accelerate myeloid recovery is considered medically appropriate if ANY ONE of the following criteria are met:
The individual has undergone an autologous bone marrow transplant (BMT) due to ANY ONE of the following:
Non-Hodgkin's lymphoma
Acute lymphoblastic leukemia
Hodgkin's disease
The individual has undergone an allogeneic bone marrow transplant (BMT) and has ALL of the following:
A diagnosis of myeloid malignancy
Received myeloablative chemotherapy
Filgrastim to prolong survival after bone marrow transplantation (BMT) is considered medically appropriate if ANY ONE the following criteria are met:
The individual has failure of myeloid engraftment
The individual has delayed myeloid engraftment
Filgrastim for the treatment of acquired immunodeficiency syndrome (AIDS) is considered medically appropriate if ALL the following criteria are met:
The individual has a diagnosis of cytomegalovirus (CMV) retinitis
The individual has been treated with ganciclovir
Pegfilgrastim
Pegfilgrastim to decrease the incidence of infection is considered medically appropriate if ALL the following criteria are met:
The individual is diagnosed with a non-myeloid malignancy
The individual is receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia (e.g., doxorubicin, docetaxel)
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
Filgrastim
A single official standard reference compendium, AHFS DI, recognizes the use of filgrastim in the treatment of:
Aplastic anemia
Myelodysplastic syndromes
Children with advanced-stage neuroblastoma receiving chemotherapy
Hematopoietic stem cell transplantation following myeloablative chemotherapy
A single official standard reference compendium, USP DI Drug Information for the Healthcare Professional (2006), recognized the use of filgrastim in the treatment of pediatric individuals with cancer who are receiving myelosuppressive chemotherapy.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
Filgrastim (Neupogen®) is produced using Escherichia coli (E coli) and is a non-glycosylated recombinant product.
Pegfilgrastim (Neulasta®) is a covalent conjugate of filgrastim and monomethoxypolyethelene glycol produced through pegylation. It has reduced renal clearance and prolonged persistence in vivo as compared to filgrastim.
No controlled studies were found in the published literature that validate the use of filgrastim or pegfilgrastim in the treatment of other conditions/diseases.
SOURCES
Amgen. (2008, April). Neulasta® (pegfilgrastim) label information. Retrieved June 9, 2008 from http://www.amgen.com/pdfs/misc/neulasta_pi.pdf.
BlueCross BlueShield Association. Medical Policy Reference Manual. (3:2002). Colony Stimulating Factors. (5.01.03). Retrieved June 9, 2008 from BlueWeb.
Lexi-Comp Online. (2008). AHFS DI. Filgrastim. Retrieved June 9, 2008 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2008). AHFS DI. Pegfilgrastim. Retrieved June 9, 2008 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2008). Filgrastim. Retrieved June 9, 2008 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2008). Pegfilgrastim. Retrieved June 9, 2008 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. USP DI Drug Information for the Healthcare Professional. (2006). Colony Stimulating Factors (Systemic). Retrieved September 26, 2006 from MICROMEDEX Healthcare Series.
Riverbend: Government Benefits Administrator, Local Coverage Determinations (LCDs). (May, 2008). LCD for Neupogen® (Filgrastim) and Neulasta ® (Pegfilgrastim) (L13239). Retrieved June 9, 2008 from https://www.cms.hhs.gov/scripts/ctredirector.dll/.pdf?@_CPR0a0a043a07d1.EO_0oxM_GZDT.
U. S. Department of Health and Human Services. Centers for Medicare & Medicaid Services. LMRPs/LCDs for Cigna Government Services. (2007, October). LCD for Colony Stimulating Factors (L24841). Retrieved June 9, 2008 from https://www.cms.hhs.gov/scripts/ctredirector.dll/.pdf?@_CPR0a0a043a07d1.SI_0ou6_uXE0.
U. S. Food and Drug Administration. (2006, October). Center for Drug Evaluation and Research. Neupogen® (Filgrastim) label information. Retrieved June 9, 2008 from http://www.fda.gov/cder/foi/label/2006/103353s5086LBL.pdf.
ORIGINAL EFFECTIVE DATE: 3/10/2005
MOST RECENT REVIEW DATE: 9/24/2008
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Granulocyte Colony Stimulating Factors (Filgrastim [Neupogen®] and Pegfilgrastim [Neulasta®])
|
Mild Neutropenia = |
Absolute neutrophil count (ANC) of 1000-2000/mm3 |
|
Moderate Neutropenia = |
ANC of 500-1000/mm3 |
|
Severe Neutropenia = |
ANC less than 500/mm3 |
Filgrastim (Neupogen®)
Is the requested agent being used for ANY ONE of the following?
Enhancement of the efficacy of myelosuppressive chemotherapy
Shortening the duration of chemotherapy
Prophylactic treatment
Adjunction to empiric anti-infective therapy with the development of febrile neutropenia secondary to chemotherapy-induced myelosuppression
To prevent subsequent episodes of febrile neutropenia secondary to chemotherapy induced myelosuppression
Treatment of hairy cell leukemia
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Is the individual receiving anti-cancer treatment with ANY ONE of the following conditions?
A non-myeloid malignancy with ALL of the following:
Increased incidence of infection as manifest by febrile neutropenia
Receiving myelosuppressive chemotherapeutic agents associated with a significant incidence of severe neutropenia (absolute neutrophil count less than 500/mm3) with fever (e.g., doxorubicin, docetaxel
Acute myelocytic leukemia with ANY ONE of the following:
Undergoing induction chemotherapy
Undergoing consolidation chemotherapy
Receiving a bone marrow transplantation with ALL of the following:
A non-myeloid malignancy
Undergoing myeloablative chemotherapy
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Is the agent being requested for mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #4
Does the individual have neutropenia of ANY ONE of the following types?
Severe chronic neutropenia (congenital, cyclic or idiopathic) with ALL of the following:
An absolute neutrophil count (ANC) of less than 500/mm3
Increased incidence and duration of clinical sequelae of neutropenia (e.g., fever, infections, and oropharyngeal ulcers)
Drug-induced neutropenia
Neutropenia associated with bone marrow transplantation (BMT)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #5
Does the individual require accelerated myeloid recovery with ANY ONE of the following?
Autologous bone marrow transplant for ANY ONE of the following:
Non-Hodgkin’s lymphoma
Acute lymphoblastic leukemia
Hodgkin’s disease
Allogeneic bone marrow transplant after ALL of the following:
A diagnosis of myeloid malignancy
Myeloablative chemotherapy
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Is the agent requested to prolong survival after bone marrow transplantation (BMT) for ANY ONE of the following?
Failure of myeloid engraftment
Delayed myeloid engraftment
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Does the individual have acquired immunodeficiency syndrome (AIDS) and ALL of the following?
Diagnosis of cytomegalovirus (CMV) retinitis
Treatment with ganciclovir
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Pegfilgrastim (Neulasta®)
Is the requested agent being used for ANY ONE of the following?
Individuals receiving antimetabolites such as 5-fluorouracil
Individuals receiving antineoplastic agents that are associated with delayed myelosuppression (e.g., nitrosoureas, mitomycin C)
Individuals receiving radiation
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Is the agent requested to decrease the incidence of infection with ALL of the following?
The individual is diagnosed with a non-myeloid malignancy
The individual is receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia (e.g., doxorubicin, docetaxel)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.