2.101 Colony-Stimulating Factors (G-CSF and GM

MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
Original Issue Date (Created):
July 1, 2002
Most Recent Review Date (Revised): January 28, 2014
Effective Date:
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
April 1, 2014
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
FDA approved colony-stimulating factors (G-CSF or GM-CSF) may be considered medically
necessary for the following uses:
 To elevate the white blood cell count in conjunction with high-dose chemotherapy with
autologous stem cell support.
 To decrease the duration of neutropenia-related sequelae (such as febrile neutropenia) in
patients with non-myeloid malignancies receiving myeloablative chemotherapy using
cancer drugs which are known to cause severe neutropenia;
 To treat patients with congenital, idiopathic or cyclic neutropenia with clinically
significant episodes of recurrent fevers, infection and/or oropharyngeal ulcers.
 Following induction chemotherapy in older adult patients with acute myelogenous
leukemia to shorten time to neutrophil recovery and to reduce the incidence of severe and
life-threatening infections;
 In patients who have undergone allogeneic or autologous bone marrow transplantation
and are experiencing graft failure or delayed engraftment in the presence or absence of
infection;
 To accelerate recovery of white blood cell counts and reduce incidence of infection after
high-dose chemotherapy with allogeneic bone marrow transplantation; and
 For use in priming collection and mobilization of peripheral blood stem cells.
Colony-stimulating factors (G-CSF or GM-CSF) may be considered medically necessary for the
following off-label use:
 To treat drug-induced neutropenia in HIV-infected patients when an alternative(s) to the
offending agent is not available, not tolerated or is less effective.
Page 1
MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101

To increase neutrophil counts in patients with myelodysplastic syndrome.

To treat neutropenia secondary to hypersplenism.
Note: Although G-CSF (e.g. Filgrastim (Neupogen) and pegfilgrastim (Neulasta) and GM-CSF
(e.g., Sargramostim (Leukine) have different FDA-approved label indications, they are
interchangeable for all FDA approved uses.
Colony-Stimulating Factors (G-CSF or GM-CSF) are considered investigational for all other
applications including the following:
 Prevention of cytopenia in patients who are scheduled for, but not receiving,
myelosuppressive chemotherapy;
 Treating chronic marrow failure (low white blood cell counts) due to prior chemotherapy
treatment; or
 To treat drug-induced neutropenias other than those causes listed above.
There is insufficient evidence to support a conclusion concerning the health outcomes or benefits
associated with this procedure for these indications.
Stem Cell Mobilizers
Plerixafor (Mozobil ®) may be considered medically necessary when used in combination with
granulocyte- colony stimulating factors (G-CSF and GM-CSF) to mobilize hematopoietic stem
cells to the peripheral blood for collection and subsequent autologous transplantation in patients
with non-Hodgkins’s lymphoma and multiple myeloma. Plerixafor (Mozobil ®) may be
considered medically necessary for treatment of the off-label indication of Hodgkin’s
lymphoma.
Plerixafor (Mozobil ®) is considered investigational for all other indications as there is
insufficient evidence to support a conclusion concerning the health outcomes or benefits
associated with this procedure for these indications.
Cross-reference:
MP-9.037 Autologous and Allogeneic Stem Cell Transplantation
MP-2.103 Off-Label Use of Prescription Drug and Medical Devices
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MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
II. PRODUCT VARIATIONS
TOP
[N] = No product variation, policy applies as stated
[Y] = Standard product coverage varies from application of this policy, see below
[N] Capital Cares 4 Kids
[N] Indemnity
[N] PPO
[N] SpecialCare
[N] HMO
[N] POS
[N] SeniorBlue HMO
[Y] FEP PPO*
[N] SeniorBlue PPO
* For Neupogen refer to FEP Medical Policy Manual MP-5.10.10
For Neulasta refer to FEP Medical Policy Manual 5.10.09
For Leukine refer to FEP Medical Policy Manual 5.10.08
The FEP Medical Policy manual can be found at: www.fepblue.org
**For Mozobil - The FEP program dictates that all drugs, devices or biological products approved by
the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore,
FDA-approved drugs, devices or biological products may be assessed on the basis of medical
necessity.
III. DESCRIPTION/BACKGROUND
TOP
Bone marrow produces different types of cells, including red and white blood cells. Certain
white blood cells (WBCs), known as granulocytes and macrophages, are part of the immune
system that the body uses to fight infections. Types of granulocytes include neutrophils,
eosinophils, and basophils. Neutropenia is a condition in which there is a lower-than-normal
number of neutrophils (i.e. less than 1500 to 2000 per microliter). Causes of neutropenia include
chemotherapy treatment and congenital or idiopathic conditions. Neutropenia can put a patient
at risk for life-threatening infections.
Under certain circumstances, the bone marrow may not be able to produce enough white blood
cells to fight infections. Granulocyte and granulocyte-macrophage colony stimulating factors
(G-CSF and GM-CSF) stimulate the bone marrow to produce white blood cells.
Examples of G-CSFs include Filgrastim (Neupogen) and pegfilgrastim (Neulasta). Pegfilgrastim
is a long-acting form of filgrastim. An example of a GM-CSFs is Sargramostim (Leukine).
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MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
These drugs are artificially produced and must be given by injection or intravenous infusion until
patients are able to produce adequate WBCs on their own.
Filgrastim has been approved by the by the U.S. Food and Drug Administration (FDA) for the
following indications: cancer patients receiving myelosuppressive chemotherapy or bone marrow
transplant, patients with acute myeloid leukemia receiving induction or consolidation
chemotherapy, patients undergoing peripheral blood progenitor cell collection/therapy and
patients with severe chronic neutropenia (e.g. congenital, cyclic, or idiopathic). Filgrastim is
administered by daily subcutaneous injections. The dose and schedule varies by clinical
condition.
Pegfilgrastim has been approved by the FDA to reduce the incidence of infection associated with
chemotherapy. The recommended dose is a single subcutaneous injection administered once per
chemotherapy cycle. Since the drug is administered at the onset of a treatment cycle, it remains
in the blood while the patient is neutropenic and before complications begin.
Sargramostim has been approved by the FDA for the following indications: following induction
chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to
neutrophil recovery, use in mobilization and following transplantation of autologous peripheral
blood progenitor cells, use in myeloid reconstitution after autologous bone marrow
transplantation, use in myeloid reconstitution after allogeneic bone marrow transplantation, and
use in bone marrow transplantation failure or engraftment delay. Filgrastim is administered by
daily subcutaneous injections. The dose and schedule varies by clinical condition.
Plerixafor (Mozobil ®) is indicated in combination with granulocyte-colony stimulating factor
(G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and
subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple
myeloma. Under certain circumstances, the bone marrow may not be able to produce enough
white blood cells to fight infections. Granulocyte and granulocyte-macrophage colony
stimulating factors (G-CSF and GM-CSF) stimulate the bone marrow to produce white blood
cells.
Mozobil treatment should begin after the patient has received G-CSF once daily for four days.
Mozobil is then administered approximately 11 hours prior to the initiation of apheresis for up to
four consecutive days. Mozibil is administered by subcutaneous injection based on 0.24 mg/kg
body weight. In patients with renal impairment, the dose of Mozobil should be decreased by
one-third to 0.16/kg.
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MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
IV. DEFINITIONS
TOP
ALLOGENEIC refers to having a different genetic constitution but belonging to the same species,
i.e., involves a donor and a recipient.
ALLOGRAFT refers to transplant tissue obtained from a member of one's own species.
AUTOLOGOUS refers to originating within an individual, i.e., self-donation.
CYTOPENIA is the diminution of cellular elements in blood or other tissue.
MYELOABLATIVE refers to treatment designed to destroy virtually all blood cells and cancer
cells.
NEUTROPENIA is the presence of an abnormally small number of neutrophils in the blood,
usually less than 1500 to 2000 per microliter.
NEUTROPHIL is a granular white blood cell (WBC), the most common type. It functions in
fighting acute infections.
OFF LABEL DRUG USE is the use of a drug to treat a condition for which it has not been
approved by the U.S. Food and Drug Administration (FDA), especially when such may relieve
unpleasant symptoms or prove compassionate. Drug effects that have been observed but not
specifically proven (and for which no application has been made) may be utilized for unproven,
or "off-label" uses by licensed medical practitioners.
V.
BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit under
the member's contract. Benefit determinations should be based in all cases on the applicable
contract language. Medical policies do not constitute a description of benefits. A member’s
individual or group customer benefits govern which services are covered, which are excluded,
and which are subject to benefit limits and which require preauthorization. Members and
providers should consult the member’s benefit information or contact Capital for benefit
information.
VI. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical
advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of
members. Members should discuss any medical policy related to their coverage or condition with their provider
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MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
and consult their benefit information to determine if the service is covered. If there is a discrepancy between this
medical policy and a member’s benefit information, the benefit information will govern. Capital considers the
information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.
VII.
CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined by the
terms of member benefit information. In addition, not all covered services are eligible for separate
reimbursement.
HCPCS
Code
Description
J1440
J1441
INJECTION, FILGRASTIM (G-CSF), 300 MCG
INJECTION, FILGRASTIM (G-CSF), 480 MCG
J2505
INJECTION, PEGFILGRASTIM, 6 MG
J2562
INJECTION, PLERIXAFOR, 1 MG
J2820
INJECTION, SARGRAMOSTIM (GM-CSF), 50 MCG
ICD-9-CM
Diagnosis
Code*
Description
042.0
HTLV-III/LAV INFECT W SPEC INFECTIONS
078.5
140.0 –
209.36
CYTOMEGALOVIRAL DISEASE
238.71
ESSENTIAL THROMBOCYTHEMIA
238.72
LOW GRADE MYELODYSPLASTIC SYNDROME LESIONS
238.73
HIGH GRADE MYELODYSPLASTIC SYNDROME LESIONS
238.74
MYELODYSPLASTIC SYNDROME WITH 5Q DELETION
238.75
MYELODYSPLASTIC SYNDROME, UNSPECIFIED
238.76
MYELOFIBROSIS WITH MYELOID METAPLASIA
238.79
OTHER LYMPHATIC AND HEMATOPOIETIC TISSUES
284.9
UNSPECIFIED APLASTIC ANEMIA
288.00
NEUTROPENIA, UNSPECIFIED
288.01
CONGENITAL NEUTROPENIA
MALIGNANT NEOPLASMS
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MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
ICD-9-CM
Diagnosis
Code*
Description
288.02
CYCLIC NEUTROPENIA
288.03
DRUG INDUCED NEUTROPENIA
288.04
NEUTROPENIA DUE TO INFECTION
288.09
OTHER NEUTROPENIA
528.0
STOMATITIS AND MUCOSITIS (ULCERATIVE)
780.6
909.5
FEVER AND OTHER PHYSIOLOGIC DISTURBANCES OF TEMPERATURE REGULATION
LATE EFFECT OF ADVERSE EFFECT OF DRUG, MEDICAL OR BIOLOGICAL
SUBSTANCE
996.85
COMPLICATIONS OF BONE MARROW TRANSPLANT
E93.17
ANTIVIRAL DRUGS CAUSING ADVERSE EFFECT IN THERAPEUTIC USE
V42.81
BONE MARROW REPLACED BY TRANSPLANT
V58.11
ENCOUNTER FOR ANTINEOPLASTIC CHEMOTHERAPY
V58.12
ENCOUNTER FOR ANTINEOPLASTIC IMMUNOTHERAPY
V59.02
STEM CELL DONOR
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
The following ICD-10 diagnosis codes will be effective October 1, 2014:
ICD-10-CM
Diagnosis
Description
Code*
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
VIII. REFERENCES
TOP
Amgen. Neupogen ® (filgrastim) prescribing information. Revised: 09/2013 [Website]:
http://pi.amgen.com/united_states/neupogen/neupogen_pi_hcp_english.pdf
. Accessed November 22, 2013.
Baehner R. Overview of neutropenia. In: UpToDate Online Journal [serial online]. Waltham,
MA: UpToDate; updated August 30, 2012. [Website]: www.uptodate.com . Accessed
November 22, 2013.
Page 7
MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
Bayer Healthcare Pharmaceuticals. Leukine® (sargramostim) product information. 07/2009.
[Website]:
http://www.leukine.com/~/media/Files/Leukine/6061%20Liquid%20Patient%20Insert%20r5.
pdf Accessed November 22, 2013.
Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual.
Publication 100-02. Chapter 15. Section 50.4.2. Unlabeled Use of Drug. Effective 10/01/03.
[Website]: http://www.cms.gov/manuals/Downloads/bp102c15.pdf . Accessed November 22,
2013.
Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual.
Publication 100-02. Chapter 15. Sections 50, 50.4.1, 50.4.3. Drugs and Biologicals.
Effective 10/01/03. [Website]: http://www.cms.gov/manuals/Downloads/bp102c15.pdf .
Accessed November 22, 2013.
Neulasta: Product Information for Professionals. 06/2011. [Website]:
http://pi.amgen.com/united_states/neulasta/neulasta_pi_hcp_english.pdf. Accessed
November 22, 2013.
Sieff C. Introduction to recombinant hematopoietic growth factors. In: UpToDate Online Journal
[serial online]. Waltham, MA: UpToDate; updated April 24, 2012. [Website]:
www.uptodate.com. Accessed November 22, 2013.
Taber’s Cyclopedic Medical Dictionary, 20h edition.
Plerixafor (Mozobil ®)
Cashen A, Lopez S, Gao F, et al. A phase II study of plerixafor (AMD3100) plus G-CSF for
autologous hematopoietic progenitor cell mobilization in patients with Hodgkin lymphoma.
Biol Blood Marrow Transplant. 2008; 14(11):1253-1261.
Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual.
Publication 100-02. Chapter 15. Section 50.4.2. Unlabeled Use of Drug. Effective 10/01/03.
[Website]: http://www.cms.gov/manuals/Downloads/bp102c15.pdf . Accessed November 22,
2013.
Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual.
Publication 100-02. Chapter 15. Sections 50, 50.4.1, 50.4.3. Drugs and Biologicals.
Effective 10/01/03. [Website]: http://www.cms.gov/manuals/Downloads/bp102c15.pdf .
Accessed November 22, 2013.
Devine SM, Vij R, Rettig M, Todt L, et al. Rapid mobilization of functional donor hematopoietic
cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood.
2008; 112(4):990-998.
Genzyme Corporation. Mozobil (plerixifor). Full Prescribing Information. Cambridge, MA:
Genzyme; Revised 6/2013. [Website]:
http://www.mozobil.com/document/Package_Insert.pdf Accessed November 22, 2013.
Page 8
MEDICAL POLICY
POLICY TITLE
COLONY-STIMULATING FACTORS (G-CSF AND GM-CSF) AND STEM CELL
MOBILIZERS
POLICY NUMBER
MP-2.101
Jin P, Wang E, et al. Differentiation of two types of mobilized peripheral blood stem cells by
microRNA and cDNA expression analysis. J Transl Med. 2008 Jul 22; 6:39.
IX. POLICY HISTORY
MP 2.101
TOP
CAC 5/25/04
CAC 6/28/05
CAC 8/30/05
CAC 5/30/06
CAC 1/30/07
CAC 3/25/08
CAC 1/27/09
CAC 11/24/09 Minor revision adding Plerixafor (Mozobil ®) to the policy.
CAC 11/30/10 Consensus no change in policy statement. References
updated.
CAC 11/22/11 Consensus review.
CAC 3/26/13 Consensus review. No change to policy statements.
References updated. (Codes reviewed.)
CAC 1/28/14 Consensus review. No change to policy statements.
References updated.
Top
Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance
Company®, Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the
BlueCross BlueShield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs
and provider relations for all companies.
Page 9

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