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Date Printed: October 17, 2017: 04:29 PM

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09-J0000-62

Original Effective Date: 11/15/00

Reviewed: 05/10/17

Revised: 07/01/17

Subject: Granulocyte Colony Stimulating Factors

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           

Position Statement

Dosage and Administration

Billing/Coding

Reimbursement

Program Exceptions

Definitions

           

Related Guidelines

Other

References

Updates

 

Previous Version

           

DESCRIPTION:

The risk of infection among patients receiving myelosuppressive chemotherapy who develop neutropenia is mitigated by two prophylactic strategies: antibiotics and myeloid growth factors. While antibiotics are generally recommended after febrile neutropenia has developed, guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend the prophylactic use of myeloid growth factors to prevent neutropenia. Agents currently approved for the reduction of febrile neutropenia risk in patients receiving myelosuppressive chemotherapy include pegfilgrastim (Neulasta®), filgrastim (Neupogen®), filgrastim-sndz (Zarxio™), tbo-filgrastim (Granix™) and sargramostim (Leukine®). Filgrastim, filgrastim-sndz, tbo-filgrastim, and pegfilgrastim are recombinant granulocyte colony-stimulating factors (G-CSFs). Sargramostim is a granulocyte-macrophage colony-stimulating factor (GM-CSF). All four agents are glycoproteins which act upon hematopoietic cells by binding to specific cell surface receptors to stimulate proliferation. In addition to being used for the prevention of febrile neutropenia, these agents are used in the treatment neutropenia in a number of clinical situations.

POSITION STATEMENT:

 

Certificate of Medical Necessity

Submit a completed Certificate of Medical Necessity (CMN) along with your request to expedite the medical review process.

1. Click the link Granulocyte Colony Stimulating Factors - Certificate of Medical Necessity (MS Word) to open the form.

2. Complete all fields on the form thoroughly.

3. Print and submit a copy of the form with your request.

Note: Florida Blue regularly updates CMNs. Ensure you are using the most current copy of a CMN before submitting to Florida Blue. For a complete list of available CMNs, visit the Certificates of Medical Necessity page.

I. The use of filgrastim (Neupogen) or pegfilgrastim (Neulasta) meet the definition of medically necessary for members meeting ALL of the following:

1. Indication for use (and any additional criteria) is listed in Table 1

2. Dose does not exceed the following and will be achieved using the fewest vials or syringes per day:

a. Filgrastim: 10 mcg/kg/day

i. Exception: 12 mcg/kg/day if indications for use is congenital neutropenia

b. Pegfilgrastim: 6 mg

Duration of approval: 1 year

II. The use of filgrastim-sndz (Zarxio), tbo-filgrastim (Granix), and sargramostim (Leukine) meet the definition of medically necessary for members meeting ALL of the following:

1. Member has inadequate response or contraindication to filgrastim (Neupogen)

2. Indication for use (and any additional criteria) is listed in Table 1

3. Dose does not exceed the following and will be achieved using the fewest vials or syringes per day:

a. Filgrastim-sndz: 10 mcg/kg/day

i. Exception: 12 mcg/kg/day if indications for use is congenital neutropenia

b. Tbo-filgrastim: 5 mcg/kg/day

c. Sargramostim: 250 mcg/meter squared/day

Duration of approval: 1 year

TABLE 1:

Criteria for use of colony stimulating factors

Indication for use

Additional Criteria

Congenital, cyclic, or idiopathic neutropenia (excludes requests for tbo-filgrastim)

Must be met:

1. Used to reduce the incidence and duration of sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with severe chronic neutropenia (SCN)

Hematopoietic stem cell transplant

ONE must be met:

1. Use as an adjunct to Peripheral Blood Progenitor Cell (PBPC) transplantation to mobilize peripheral stem cells when bone marrow transplant is a covered benefit

2. Myeloid engraftment following hematopoietic stem cell transplant

3. Reduce severity of neutropenia in members with non-myeloid malignancies undergoing myeloablative chemotherapy followed by autologous or allogeneic bone marrow transplant

4. Delayed or failed engraftment in members who have undergone allogeneic or autologous hematopoietic stem cell transplant

Hematopoietic Syndrome of Acute Radiation Syndrome (excludes requests for tbo-filgrastim)

Must be met:

1. Used to increase survival in members acutely exposed to myelosuppressive doses of radiation

Myelodysplastic syndrome (excludes requests for pegfilgrastim and sargramostim)

ONE of the following:

1. Member is experiencing recurrent or resistant infections

2. Use is in combination with epoetin alfa or darbepoetin alpha when erythropoietin levels are 500 mUnits/mL or less

Prevention of febrile neutropenia (excludes requests for sargramostim)

ONE must be met:

1. Receiving myelosuppressive regimen at high-risk of febrile neutropenia with expected incidence greater than 20%

2. Febrile neutropenia or dose-limiting neutropenic event in earlier chemotherapy cycle

3. Receiving myelosuppressive chemotherapy with an intermediate-risk (10-20%) of febrile neutropenia, AND presence of at least one or more of the following:

a. Age greater than 65 years

b. Prior chemotherapy or radiation therapy

c. Persistent neutropenia

d. Bone marrow involvement by tumor

e. Recent surgery and/or open wounds

f. Liver dysfunction (bilirubin greater than 2 mg/dL)

g. Renal dysfunction (creatinine clearance less than 50 ml/min)

h. HIV infection

i. Chronic immunosuppression in the transplant setting

j. Poor performance status

Treatment of chemotherapy-induced febrile neutropenia (excludes requests for pegfilgrastim)

ONE of the following:

1. Member was receiving prophylactic therapy with ONE of the following: filgrastim (Neupogen), filgrastim-sndz (Zarxio), tbo-filgrastim (Granix)

2. Member did not receive prophylactic therapy and has ONE of the following risk factors:

a. Sepsis syndrome

b. Age greater than 65 years

c. Absolute neutrophil count less than 100/microL

d. Neutropenia expected more than 10 days duration

e. Pneumonia or other infection

f. Invasive fungal infection

g. Hospitalization at time of fever

h. Prior episode of febrile neutropenia

Treatment (or adjunctive treatment) of neutropenia (excludes requests for tbo-filgrastim)

ONE must be met:

1. HIV infection

1. Nonmalignant condition AND receiving myelosuppressive drug

2. Acute myelogenous leukemia (AML) in adults receiving chemotherapy (induction or consolidation)

Filgrastim, pegfilgrastim, tbo-filgrastim, filgrastim-sndz, and sargramostim are considered experimental or investigational when administered for all other indications, as there is insufficient clinical evidence to support their use.

NOTE: Dose-dense regimens (treatment given more frequently), specifically in the treatment of node positive breast cancer, small cell lung cancer, and diffuse aggressive non-Hodgkin’s lymphoma will be considered.

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

Dosage is based on body weight and varies dependent upon response, product selected, and indication. Refer to product-specific labeling for complete dosing and administration instructions.

Filgrastim, filgrastim-sndz, tbo-filgrastim

Should not be administered in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy.

Pegfilgrastim

Should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Sargramostim

Should not be administered in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy or radiation therapy.

PRECAUTIONS:

Contraindications

Filgrastim, filgrastim-sndz, pegfilgrastim, tbo-filgrastim

Contraindicated in patients with a history of serious allergic reactions to other granulocyte colony-stimulating factors

Sargramostim

Contraindicated in patients with excessive leukemic myeloid blasts in the bone marrow or peripheral blood (≥ 10%), in patients with known hypersensitivity to GM-CSF, yeast-derived products or any component of the product, and in concomitant use with chemotherapy and radiotherapy.

Precautions/Warnings

Filgrastim, filgrastim-sndz, pegfilgrastim, tbo-filgrastim

Splenic Rupture - Splenic rupture, including fatal cases, has been reported. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

Acute Respiratory Distress Syndrome - Acute respiratory distress syndrome (ARDS) has been reported. Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue in patients with ARDS.

Serious Allergic Reactions - Serious allergic reactions, including anaphylaxis, have been reported. The majority of reported events occurred upon initial exposure. Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue in patients with serious allergic reactions.

Sickle Cell Disorders - Sickle cell crisis, in some cases fatal, has been reported in patients with sickle cell trait or sickle cell disease.

Glomerulonephritis - Glomerulonephritis has occurred. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose reduction or discontinuation. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption.

Alveolar Hemorrhage and Hemoptysis - Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation.

Capillary Leak Syndrome - Capillary leak syndrome (CLS) has been reported after G-CSF administration, and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

Severe Chronic Neutropenia - Myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. Cytogenetic abnormalities, transformation to MDS, and AML have also been observed. If a patient develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing therapy should be carefully considered.

Thrombocytopenia - Thrombocytopenia has been reported. Monitor platelet counts.

Leukocytosis - In patients with cancer receiving therapy as an adjunct to myelosuppressive chemotherapy‚ to avoid the potential risks of excessive leukocytosis‚ it is recommended that therapy be discontinued if the ANC surpasses 10‚000/mm after the chemotherapy-induced ANC nadir has occurred. Monitor CBCs at least twice weekly during therapy. Dosages that increase the ANC beyond 10‚000/mm may not result in any additional clinical benefit. During the period of administration for PBPC mobilization in patients with cancer, discontinue if the leukocyte count rises to > 100,000/mm.

Cutaneous Vasculitis - Cutaneous vasculitis has been reported. In most cases‚ the severity of cutaneous vasculitis was moderate or severe. Hold therapy in patients with cutaneous vasculitis.

Potential Effect on Malignant Cells - The possibility that GCS-F acts as a growth factor for any tumor type cannot be excluded

Simultaneous Use with Chemotherapy and Radiation Therapy Not Recommended - The safety and efficacy of GCS-F given simultaneously with cytotoxic chemotherapy or in patients receiving concurrent

radiation therapy has not been established. Avoid the simultaneous use with chemotherapy and radiation therapy.

Nuclear Imaging - Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes. This should be considered when interpreting bone-imaging results.

Sargramostim

Pediatric Use - Benzyl alcohol is a constituent of sargramostim has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. Do not administer to neonates.

Fluid Retention - Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported. Use with caution in patients with preexisting fluid retention, pulmonary infiltrates or congestive heart failure.

Respiratory Symptoms - Sequestration of granulocytes in the pulmonary circulation has been documented; infusion and dyspnea has been reported occasionally. In patients displaying dyspnea during administration, the rate of infusion should be reduced by half. If respiratory symptoms worsen despite infusion rate reduction, the infusion should be discontinued.

Cardiovascular Symptoms - Occasional transient supraventricular arrhythmia has been reported.

Renal and Hepatic Dysfunction - In some patients with preexisting renal or hepatic dysfunction,

elevation of serum creatinine or bilirubin and hepatic enzymes occurred. Dose reduction or interruption has resulted in a decrease to pretreatment values.

Serious allergic or anaphylactic reactions or syndrome - If any serious allergic or anaphylactic reaction occurs, discontinue and initiate appropriate therapy. A syndrome characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia has been reported following the first administration.

Leukocytosis - Stimulation of marrow precursors may result in a rapid rise in white blood cell (WBC)

count. If the ANC exceeds 20,000 cells/mm or if the platelet count exceeds 500,000/mm, administration should be interrupted or the dose reduced by half.

Growth Factor Potential - Because of the possibility of tumor growth potentiation, precaution

should be exercised when using this drug in any malignancy with myeloid characteristics.

BILLING/CODING INFORMATION:

The following codes may be used to report these services:

HCPCS Coding:

J1442

Injection, filgrastim (G-CSF), excludes biosimilars,1 microgram

J1447

Injection, tbo-filgrastim, 1 microgram

J2505

Injection, pegfilgrastim, 6mg (Neulasta®)

J2820

injection, sargramostim (GM-CSF), 50 mcg (Leukine®)

Q5101

Injection, filgrastim (G-CSF), biosimilar, 1 microgram

ICD-10 Diagnoses Codes That Support Medical Necessity for Filgrastim (Neupogen®), Filgrastim-sndz (Zarxio™), Pegfilgrastim (Neulasta®), and Sargramostim (Leukine®):

B20

Human immunodeficiency virus [HIV] disease

C00-0 – C02.9

Malignant neoplasm of lip, base of tongue and other and unspecified parts of the tongue

C03.0 – C06.9

Malignant neoplasm of gum, floor of mouth, palate and other and unspecified parts of mouth

C07 – C08.9

Malignant neoplasm of other and unspecified major salivary glands

C09.0 – C11.9

Malignant neoplasm of tonsil, oropharynx and nasopharynx

C12 – C26.9

Malignant neoplasm of pyriform sinus, hypopharynx and other and ill-defined sites in the lip, oral cavity and pharynx, esophagus, stomach, small intestine, colon, rectosigmoid junction, rectum, anus and anal canal, liver and intrahepatic bile ducts, gallbladder, other and unspecified parts of biliary tract, pancreas and other and ill-defined digestive organs

C30.0 – C34.9

Malignant neoplasm of nasal cavity and middle ear, accessory sinuses, larynx, trachea and bronchus and lung

C37 – C39.9

Malignant neoplasm of thymus, heart, mediastinum and pleura, and other and ill-defined sites in the respiratory system

C40.00 – C41.9

Malignant neoplasm of bone and articular cartilage of limbs and other and unspecified sites

C43.0 – C44.9

Malignant melanoma of skin and other malignant neoplasm of skin

C46.0 – C46.9

Kaposi's sarcoma

C48 – C48.9

Malignant neoplasm of retroperitoneum and peritoneum

C49.0 – C49.9

Malignant neoplasm of other connective and soft tissue

C49.A0 – C49.A9

Gastrointestinal stromal tumor

C50.0 – C50.929

Malignant neoplasm of breast

C51.0 – C68.0

Malignant neoplasm of vulva, vagina, cervix uteri, corpus uteri, uterus, part unspecified, ovary, other and unspecified female genital organs, placenta, penis, prostate, testis, other and unspecified male genital organs, kidney, except renal pelvis, renal pelvis, ureter, bladder and other and unspecified urinary organs

C69.00 – C69.92

Malignant neoplasm of eye and adnexa

C71.0 – C75.09

Malignant neoplasm of brain, spinal cord, cranial nerves and other parts of central nervous system, thyroid gland, adrenal gland and other endocrine glands and related structures

C76.0 – C80.2

Malignant neoplasm of other and ill-defined sites and secondary and unspecified malignant neoplasm of lymph, respiratory and digestive organs, other and unspecified sites and without specification of site

C7A.00 – C7.A8

C7B.00 – C7.B8

Malignant neuroendocrine tumors

C81.00 – C83.99

Hodgkin, follicular and non-follicular lymphoma

C88.0

Waldenstrom macroglobulinemia

C88.8

Other malignant immunoproliferative diseases

C90.00 – C92.92

Multiple myeloma and malignant plasma cell neoplasms, lymphoid and myeloid leukemia

C94.40 – C94.42

Acute panmyelosis with myelofibrosis

D03.0 – D03.9

Melanoma in situ

D45 – D48.9

Polycythemia Vera, myelodysplastic syndromes, other neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue and uncertain behavior of other and unspecified sites

D49.0 – D49.9

Neoplasms of unspecified behavior

D61.1

Drug-induced aplastic anemia

D61.2

Aplastic anemia due to other external agents

D61.89

Other specified aplastic anemias and other bone marrow failure syndromes

D70.0 – D70.9

Neutropenia

E40 – E60

Kwashiorkor, nutritional marasmus, marasmic kwashiorkor, unspecified severe protein-calorie malnutrition, protein-calorie malnutrition of moderate and mild degree, retarded development following protein-calorie malnutrition, unspecified protein-calorie malnutrition, vitamin A deficiency, thiamine deficiency, niacin deficiency (pellagra) deficiency of other B group vitamins, vitamin D deficiency, other vitamin deficiencies, dietary calcium deficiency, dietary selenium deficiency and dietary zinc deficiency

E61.4 – E61.5

Chromium and molybdenum deficiency

T36.0 – T50.996

Poisoning by, adverse effect of and underdosing of systemic antibiotics, underdosing of other systemic anti-infectives and antiparasitics, hormones and their synthetic substitutes and antagonists, not elsewhere classified, nonopioid analgesics, antipyretics and antirheumatics, narcotics and psychodysleptics (hallucinogens), anesthetics and therapeutic gases, antiepileptic, sedative-hypotonic and antiparkinsonism drugs, primarily affecting the autonomic nervous system, primarily systemic and hematological agents, not elsewhere classified, primarily affecting the cardiovascular system, primarily affecting the gastrointestinal system, primarily acting on smooth and skeletal muscles and the respiratory system, topical agents primarily affecting skin and mucous membrane and by ophthalmological, otorhinorlaryngological and dental drugs and diuretics and other and unspecified drugs, medicaments and biological substances (INITIAL ENCOUNTER)

T86.00 – T86.02

Unspecified complication of bone marrow transplant, rejection or failure

T86.09

Other complications of bone marrow transplant

Z41.8

Encounter for other procedures for purposes other than remedying health state

Z48.298

Encounter for aftercare following other organ transplant

Z51.11

Encounter for antineoplastic chemotherapy

Z51.89

Encounter for other specified aftercare

Z52.001

Unspecified donor, stem cells

Z52.3

Bone marrow donor

Z52.89

Donor of other specified organs or tissues

Z52.091

Other blood donor stem cells

Z94.6

Bone transplant status

Z94.81

Bone marrow transplant status

Z94.84

Stem cells transplant status

Z94.9

Transplanted organ and tissue status, unspecified

ICD-10 Diagnoses Codes That Support Medical Necessity for Tbo-Filgrastim (Granix™):

C92.1

Chronic myeloid leukemia

D46.0 – D46.9

Myelodysplastic syndromes

D46.A

Refractory cytopenia with multilineage dysplasia

D46.B

Refractory cytopenia with multilineage dysplasia and ring sideroblasts

D46.Z

Other myelodysplastic syndromes

D70.0 – D70.9

Neutropenia

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage products: No National Coverage Determination (NCD) was found at the time of the last guideline revised date. The following Local Coverage Determination (LCD) was reviewed on the last guideline revised date: G-CSF (Neupogen, Granix, Zarxio) (L34002), Pegfilgrastim (Neulasta) (L33747), and Sargramostim (GM-CSF, Leukine) (L34020) located at fcso.com.

DEFINITIONS:

Chemotherapy dose maintenance: is defined as attempts to maintain administration of chemotherapy at full doses on a specific, planned schedule.

Chemotherapy dose modification or reduction: is defined as attenuation in dose or delay in delivery of chemotherapy because of the occurrence of excessive toxicity in a prior cycle of treatment.

Curative chemotherapy: is defined as that with a high probability of cure, such as combination therapy for testicular cancer, Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), or acute leukemia.

Dose-intense chemotherapy: is treatment given at higher doses or on a more frequent schedule than is conventional in an attempt to induce either more complete remissions or a greater cure rate.

Febrile neutropenia: is generally designated as a temperature of approximately 38.5°C (greater than approx. & lt: 101°F) or greater, sustained for more than 1 hour, and developing concurrently with absolute neutropenia of less than 500 cells/µL. These combined criteria are generally the impetus for initiation of antibiotic therapy, often with hospitalization.

Neutropenia: A hematological disorder characterized by an abnormally low number of neutrophil granulocytes (a type of white blood cell).

Non-myeloid malignancy: All cancers other than myeloid leukemias. Non-myeloid cancers include all types of carcinoma, all types of sarcoma, melanoma, lymphomas, lymphocytic leukemias (ALL and CLL), and multiple myeloma.

Palliative chemotherapy: is that given in an attempt to prolong survival or relieve symptoms but without chance of cure.

Progenitor cell: A progenitor cell, often confused with stem cell, is an early descendant of a stem cell that can only differentiate, but it cannot renew itself anymore. In contrast, a stem cell can renew itself (make more stem cells by cell division) or it can differentiate (divide and with each cell division evolve more and more into different types of cells). A progenitor cell is often more limited in the kinds of cells it can become than a stem cell. In scientific terms, it is said that progenitor cells are more differentiated than stem cells.

Progenitor-cell support: refers to transplantation of hematopoietic cells derived from either the bone marrow or the peripheral blood as a means to increase patient safety and tolerance of treatment when very high doses of chemotherapy are administered to increase remission rates and increase disease-free survival (DFS).

Standard-dose chemotherapy: is treatment with a regimen of chemotherapy given at doses and intervals that have become generally accepted by practicing oncologists.

Stem Cell: a type of undifferentiated cell with the ability to divide and proliferate to form precursor cells that can differentiate into more specialized cells.

RELATED GUIDELINES:

None.

OTHER:

Laboratory Monitoring

To assess a patient’s hematologic status and ability to tolerate myelosuppressive chemotherapy, a complete blood count and platelet count should be obtained before chemotherapy is administered. Regular monitoring of hematocrit value and platelet count is recommended.

Chemotherapy Regimens and Risk for Febrile Neutropenia

Examples of Chemotherapy Regimens with a High Risk of Febrile Neutropenia (>20%)

1. Acute Lymphoblastic Leukemia (ALL)

a. ALL induction regimens

2. Bladder Cancer

a. Dose-dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)

3. Breast Cancer

a. Docetaxel + trastuzumab

b. Dose-dense AC followed by T (doxorubicin, cyclophosphamide, paclitaxel)

c. TAC (docetaxel, doxorubicin, cyclophosphamide)

d. TC (docetaxel, cyclophosphamide)

e. TCH (docetaxel, carboplatin, trastuzumab)

4. Esophageal and Gastric Cancers

a. Docetaxel/cisplatin/fluorouracil

5. Hodgkin Lymphoma

a. BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)

6. Kidney Cancer

a. Doxorubicin/gemcitabine

7. Non-Hodgkin’s Lymphoma

a. EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)

b. ICE (ifosfamide, carboplatin, etoposide)

c. RICE (rituximab, ifosfamide, carboplatin, etoposide)

d. CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone) ± rituximab

e. MINE (mesna, ifosfamide, novatrone, etoposide)

f. DHAP (dexamethasone, cisplatin, cytarabine)

g. ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine)

h. HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) + rituximab

8. Melanoma

a. Dacarbazine-based combination (dacarbazine, cisplatin, vinblastine)

b. Dacarbazine-based combination with IL-2, interferon alfa (dacarbazine, cisplatin, vinblastine, IL-2, interferon alfa)

9. Multiple Myeloma

a. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide)

b. VTD-PACE (DT-PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) + bortezomib)

10. Ovarian Cancer

a. Topotecan

b. Paclitaxel

c. Docetaxel

11. Soft Tissue Sarcoma

a. MAID (mesna, doxorubicin, ifosfamide, dacarbazine)

b. Doxorubicin

c. Ifosfamide/doxorubicin

12. Small Cell Lung Cancer

a. Topotecan

13. Testicular Cancer

a. VeIP (vinblastine, ifosfamide, cisplatin)

b. VIP (etoposide, ifosfamide, cisplatin)

c. BEP (bleomycin, etoposide, cisplatin)

d. TIP (paclitaxel, ifosfamide, cisplatin)

Examples of Chemotherapy Regimens with an Intermediate Risk of Febrile Neutropenia (10-20%)

1. Occult Primary – Adenocarcinoma

a. Gemcitabine/docetaxel

2. Breast Cancer

a. Docetaxel

b. CMF classic (cyclophosphamide, methotrexate, fluorouracil)

c. AC (doxorubicin, cyclophosphamide) + sequential docetaxel

d. AC + sequential docetaxel + trastuzumab

e. FEC (fluorouracil, epirubicin, cyclophosphamide) + sequential docetaxel

f. Paclitaxel every 21 days

g. TC (docetaxel, cyclophosphamide)

3. Cervical cancer

a. Cisplatin/topotecan

b. Paclitaxel/cisplatin

c. Topotecan

d. Irinotecan

4. Colorectal Cancer

a. FOLFOX (fluorouracil, leucovorin, oxaliplatin)

5. Esophageal and Gastric Cancers

a. Irinotecan/cisplatin

b. Epirubicin/cisplatin/ 5-fluorouracil

c. Epirubicin/cisplatin/capecitabine

6. Non-Hodgkin’s Lymphomas

a. EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)

b. EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) + IT chemotherapy

c. ACOD (modified CHOP-doxorubicin, cyclophosphamide, vincristine, prednisone)

d. GDP (gemcitabine, dexamethasone, cisplatin/carboplatin)

e. GDP (gemcitabine, dexamethasone, cisplatin) + rituximab

f. FMR (fludarabine, mitoxantrone, rituximab)

g. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab, including regimens with pegylated liposomal doxorubicin or mitoxantrone substituted for doxorubicin

7. Non-Small Cell Lung Cancer

a. Cisplatin/paclitaxel

b. Cisplatin/vinorelbine

c. Cisplatin/docetaxel

d. Cisplatin/etoposide

e. Carboplatin/paclitaxel

f. Docetaxel

8. Ovarian Cancer

a. Carboplatin/docetaxel

9. Pancreatic Cancer

a. FOLFIRINOX

10. Prostate Cancer

a. Cabazitaxel

11. Small Cell Lung Cancer

a. Etoposide/carboplatin

12. Testicular Cancer

a. Etoposide/cisplatin

13. Uterine Sarcoma

a. Docetaxel

REFERENCES:

  1. American Society of Clinical Oncology. Recommendations for the use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2015; 33:3199-3212. Amgen Inc. NEULASTA (pegfilgrastim) injection. 2016 [cited 2016 Mar 25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fdfe5d72-6b80-435a-afa4-c5d74dd852ce/.
  2. Amgen Inc. NEUPOGEN (filgrastim) injection, solution. 2017 [cited 2017 Apr 26]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=97cc73cc-b5b7-458a-a933-77b00523e193/.
  3. Cephalon Inc. GRANIX (tbo-filgrastim) injection, solution. 2017 [cited 2017 Apr 26]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=df918ec2-0907-443f-a52a-b72866959644/.
  4. Clinical Pharmacology [Internet Database]. Gold Standard, Inc., 2017 [cited 2017 Apr 20]. Available from: http://www.clinicalpharmacology-ip.com/.
  5. DRUGDEX® System [Internet Database]. Greenwood Village, Colo: Thomson Micromedex. 2017 [cited 2017 Apr 20]. Available from: http://www.thomsonhc.com/.
  6. Herbst C, Naumann F, Bohlius J, Skoetz N, Monsef I, Engert A. Antibiotics plus colony stimulating factors (CSFs) versus CSFs alone and antibiotics plus CSFs versus no prophylaxis for the prevention of infections in cancer patients receiving myelosuppressive chemotherapy or haematopoetic stem cell transplantation. Cochrane Database of Systematic Reviews 2009(4).
  7. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/mds.pdf. Accessed 4/26/17.
  8. NCCN Myeloid Growth Factor Practice Guidelines in Oncology, v2.2016; 2017 [cited 2017 Apr 26]. Available from: http://www.nccn.org/professionals/physician_gls/PDF/myeloid_growth.pdf
  9. Orphan Drug Designations and Approval [Internet Database]. U.S. Food and Drug Administration, 2017 [cited 2017 Apr 20]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  10. Sandoz. ZARXIO (filgrastim-sndz) injection, solution. 2017 [cited 2017 Apr 26]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe707775-a0ae-41b5-a744-28c41889fce8
  11. Sanofi-Aventis US LLC. LEUKINE (sargramostim) injection, powder, for solution. 2017 [cited 2017 Apr 26]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=04765fbf-f005-43aa-a628-5cc3d80f91e7/.
  12. Smith TJ, Khatcheressian J, Lyman GH, et al. 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):3187-3205.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/10/17.

GUIDELINE UPDATE INFORMATION:

11/15/00

New Medical Coverage Guideline.

12/15/02

Reviewed with no revisions.

08/15/05

Updated when services are covered, dosage and administration, when services are not covered, ICD-9 codes, definitions and references.

01/15/06

ICD-9 code update: deleted expired code V58.1, added new code V58.11.

07/01/06

Updated MCG number from 09-A9140-13 to 09-J0000-62.

09/15/06

Biennial review; excluded Medicare Advantage and updated references.

01/01/07

MCG revised to include Medicare Part D as a program exception.

09/15/07

Review and revision to guideline; consisting of renaming guideline, reformatted guideline, added indications, updated ICD-9 coding, removed Medicare Advantage from exceptions, updated internet links and updated references.

09/15/08

Review and revision to guideline; consisting of renaming guideline, updating description section, incorporating pegfilgrastim, reformatting position statement, changing dosage and administration section, adding precautions section, updating coding, definitions and references.

10/15/08

Revision to guideline; consisting of combining diagnoses for all three GCSFs.

04/15/09

Revision to guideline; consisting of adding ICD-9 codes and maximum dosages.

09/15/09

Review and revision to guideline; consisting of updating references.

10/15/09

Revision to guideline; consisting of clarifying dosage.

06/15/10

Review and revision to guideline; consisting of updating references and an adding a note to the position statement.

10/01/10

Revision to guideline; consisting of updating codes.

11/15/10

Revision to guideline consisting of formatting changes.

06/15/11

Review and revision to guideline; consisting of updating precautions, coding and references.

06/15/12

Review and revision to guideline; consisting of updating references.

05/15/13

Review and revision to guideline; consisting of updating references and formatting changes.

01/01/14

Revision to guideline; consisting of coding update.

03/15/14

Revision to guideline; consisting of description, position statement, dosage/administration, and references.

05/15/14

Review and revision to guideline; consisting of updating the description, position statement, billing/coding information, program exceptions and references.

05/15/15

Review and revision to guidelines; consisting of updating references, revision position statement.

07/01/15

Revision to guidelines; consisting of HCPCS code update.

07/15/15

Revision to guideline; removed adalimumab from CMN text in position statement.

10/01/15

Revision consisting of update to Program Exceptions section.

11/01/15

Revision: ICD-9 Codes deleted.

11/15/15

Revision consisting of update to position statement.

12/15/15

Revision consisting of update to position statement.

01/01/16

Annual HCPCS coding update: added code J1447, deleted code J1446, and revised descriptor for code J1442.

05/15/16

Review and revision to guideline; consisting of updating position statement, precautions, coding and references.

10/01/16

Update to ICD-10 codes.

07/01/17

Review and revision to guideline; consisting of updating position statement, coding and references.

Date Printed: October 17, 2017: 04:29 PM