Filgrastim and Pegfilgrastim
DESCRIPTION
Filgrastim is a recombinant granulocyte colony stimulating factor (rG-CSF). Colony stimulating factors (CSFs) are naturally occurring cytokine glycoproteins classified as immunomodulators. They serve as growth factors specifically for myeloid hematopoietic cells. A granulocyte colony stimulating factor (G-CSF) specifically modulates neutrophils and their precursors, regulating their production within the bone marrow and affecting neutrophil progenitor proliferation, differentiation and selected end-cell functional activation.
Pegfilgrastim is the pegylated form of filgrastim in which molecules are covalently linked to methoxypolyethylene glycol through the process of pegylation. This stabilizes the filgrastim molecules and protects them from enzymatic and phagocytic degradation. Filgrastim is thus allowed to remain active within the body for a longer period of time.
An example of filgrastim is Neupogen®
An example of pegfilgrastim is Neulasta®.
REFER TO DECISION SUPPORT TREE
POLICY
Filgrastim
Filgrastim for the prevention and treatment of neutropenia is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Filgrastim for the treatment of individuals undergoing peripheral blood progenitor cell (PBPC) collection through leukapheresis for autologous transplantation is considered medically necessary.
Filgrastim for the acceleration of myeloid engraftment following autologous peripheral blood progenitor cell (PBPC) transplantation is considered medically necessary.
Filgrastim for the treatment/prevention of other conditions/diseases, including, but not limited to, the treatment of hairy cell leukemia is considered investigational. (See Applicable Tennessee State Mandate Requirements below.)
Pegfilgrastim
Pegfilgrastim for the prevention and treatment of neutropenia is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Pegfilgrastim for the treatment/prevention of other conditions/diseases is considered investigational. (See Applicable Tennessee State Mandate Requirements below.)
MEDICAL APPROPRIATENESS
Filgrastim
Filgrastim for the prevention and treatment of neutropenia is considered medically appropriate if ANY ONE of the following criteria are met:
Individual has ANY ONE of the following diagnoses:
Non-myeloid malignancy with ANY ONE of the following:
Receiving myelosuppressive chemotherapeutic agents associated with a significant incidence of severe neutropenia (absolute neutrophil count less than 500/mm3) (e.g., doxorubicin, docetaxel)
Undergoing myoablative chemotherapy prior to bone marrow transplantation
Acute myeloid leukemia (AML) having received ANY ONE of the following:
Induction chemotherapy treatment
Consolidation chemotherapy treatment
Severe chronic neutropenia with ALL of the following:
Disease type is ANY ONE of the following:
Symptomatic congenital neutropenia
Symptomatic cyclic neutropenia
Symptomatic idiopathic neutropenia
Individual has/has history of ALL of the following:
Absolute neutrophil count (ANC) of less than 500/mm3
Increased incidence and duration of clinical sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers)
Acquired immunodeficiency syndrome (AIDS) with ALL of the following:
Diagnosis of cytomegalovirus (CMV) retinitis
Received treatment with ganciclovir
Drug-induced neutropenia
Neutropenia associated with bone marrow transplantation (BMT)
Individual has undergone a bone marrow transplant (BMT) with ANY ONE of the following:
Failure of myeloid engraftment
Delayed myeloid engraftment
Pegfilgrastim
Pegfilgrastim for the prevention and treatment of neutropenia is considered medically appropriate if ALL \the following criteria are met:
Diagnosis of a non-myeloid malignancy
Receiving myelosuppressive chemotherapeutic agents associated with a significant incidence of severe neutropenia (absolute neutrophil count less than 500/mm3) (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
The American Hospital Formulary Service Drug Information (AHFS DI) recognizes the use of filgrastim in the treatment of:
Aplastic anemia
Hairy Cell leukemia
Drugdex recognizes the use of filgrastim in the treatment of leukemia as an alternative or adjunct to donor leukocyte infusions in patients with leukemic relapses after allogeneic stem-cell transplantation
The NCCN Drugs & Biologics Compendium recognizes additional uses for filgrastim beyond the FDA-approved labeling in the treatment of:
Myelodysplastic syndromes with symptomatic anemia in combination with epoetin alfa or darbepoetin alfa
Prevention of neutropenia in patients with solid tumors and nonmyeloid malignancies with intermediate-risk (10% to 20% risk) and low-risk (less than 10% risk) of febrile neutropenia
(Refer to the NCCN Drugs & Biologics Compendium or NCCN Clinical Practice Guidelines for detailed recommendations)
Pegfilgrastim
A randomized phase III placebo controlled trial recognizes the use of pegfilgrastim after autologous peripheral blood stem cell transplantation.
Drugdex recognizes the use of pegfilgrastim in the harvesting of peripheral blood stem cells, prior to autologous stem-cell transplantation.
The NCCN Drugs & Biologics Compendium recognizes additional uses for pegfilgrastim beyond the FDA-approved labeling in the prevention of neutropenia in patients with solid tumors and nonmyeloid malignancies with intermediate-risk (10% to 20% risk) and low-risk (less than 10% risk) of febrile neutropenia. (Refer to the NCCN Drugs & Biologics Compendium or NCCN Clinical Practice Guidelines for detailed recommendations).
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
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).
No controlled studies were found in the published literature that validate the use of filgrastim or pegfilgrastim in the prevention or treatment of any other conditions/diseases.
SOURCES
Amgen, Inc. (2008, November). Neulasta® (pegfilgrastim). Retrieved February 15, 2010 from http://www.neulasta.com/pdf/Neulasta_PI.pdf.
Gerds, A., Fox-Geiman, M., Dawravoo, K., Rodriguez, T., Toor, A., Smith. S. et al. (2009). Randomized phase III trial of pegfilgrastim versus filgrastim after autologous peripheral blood stem cell transplantation. Biology of Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2009.12.531.
Lexi-Comp Online. (2010). AHFS DI. Filgrastim. Retrieved January 26, 2010 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2010). AHFS DI. Pegfilgrastim. Retrieved January 26, 2010 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). Filgrastim. Retrieved January 26, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). Pegfilgrastim. Retrieved January 26, 2010 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2010). NCCN Drugs & Biologics Compendium™. Filgrastim. Retrieved January 26, 2010 from the National Comprehensive Cancer Network.
National Comprehensive Cancer Network. (2010). NCCN Drugs & Biologics Compendium™. Pegfilgrastim. Retrieved January 26, 2010 from the National Comprehensive Cancer Network.
U. S. Food and Drug Administration. (2006. October). Center for Drug Evaluation and Research. Neupogen® (filgrastim). Retrieved February 10, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/103353s5086LBL.pdf.
U. S. Food and Drug Administration. (2007. July). Center for Drug Evaluation and Research. Neulasta® (pegfilgrastim) approval letter. Retrieved February 10, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/125031s091s105ltr.pdf.
U. S. Food and Drug Administration. (2007. July). Center for Drug Evaluation and Research. Neulasta® (pegfilgrastim). Retrieved February 10, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/125031s082lbl.pdf.
ORIGINAL EFFECTIVE DATE: 3/10/2005
MOST RECENT REVIEW DATE: 8/14/2010
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
Filgrastim and Pegfilgrastim (Neupogen® and Neulasta®)
Filgrastim
Is the requested medication being used to treat 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 undergoing peripheral blood progenitor cell (PBPC) collection through leukapheresis for autologous transplantation?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Did the individual receive autologous peripheral blood progenitor cell (PBPC) transplantation?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #4
Does the individual have a diagnosis of a non-myeloid malignancy and is ANY ONE of the following?
Receiving myelosuppressive chemotherapeutic agents associated with a significant incidence of severe neutropenia (absolute neutrophil count less than 500/mm3) (e.g., doxorubicin, docetaxel)
Undergoing myoablative chemotherapy prior to bone marrow transplantation
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #5
Does the individual have a diagnosis of acute myeloid leukemia (AML) and received induction or consolidation chemotherapy?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Does the individual have a diagnosis of symptomatic severe chronic neutropenia that is congenital, cyclic or idiopathic and currently or historically has ALL of the following?
Absolute neutrophil count (ANC) of less than 500/mm3
Increased incidence and duration of clinical sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Does the individual have a diagnosis of acquired immunodeficiency syndrome (AIDS) with ALL of the following?
Diagnosis of cytomegalovirus (CMV) retinitis
Received treatment with ganciclovir
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #8
Does the individual show evidence of drug-induced neutropenia or neutropenia associated with bone marrow transplantation (BMT)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #9
Has the individual has undergone a bone marrow transplant (BMT) and experienced failure of myeloid engraftment or delayed myeloid engraftment?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Pegfilgrastim
Does the individual have a diagnosis of a non-myeloid malignancy and is receiving myelosuppressive chemotherapeutic agents associated with a significant incidence of severe neutropenia (absolute neutrophil count less than 500/mm3) (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.