Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Pegfilgrastim (Neulasta®) and Related Biosimilars

Policy #:08.01.32b

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

Pegfilgrastim (Neulasta®) and related biosimilars are considered medically necessary and, therefore, covered when used as recommended by the then-current NCCN and ASCO guidelines for any of the following indications:
  • Prophylaxis of myelosuppressive chemotherapy-induced febrile neutropenia or other dose-limiting neutropenic events in high-risk (>20% risk of febrile neutropenia) individuals with solid tumors and nonmyeloid malignancies receiving treatment in the curative/adjuvant or palliative settings
  • Prophylaxis of myelosuppressive chemotherapy-induced febrile neutropenia or other dose-limiting neutropenic events in intermediate-risk (10% to 20% risk of febrile neutropenia) 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:
    • prior chemotherapy or radiation therapy
    • persistent neutropenia
    • bone marrow involvement by tumor producing cytopenias
    • recent surgery and/or open wounds
    • liver dysfunction (bilirubin greater than 2 mg/dL)
    • renal dysfunction (creatinine clearance less than 50 mL/min)
    • age greater than 65 years receiving full chemotherapy dose intensity
    • poor performance status (Eastern Cooperative Oncology Group [ECOG] Performance Status 3-4)
    • HIV infection with low CD4 counts (450 cells/mm3 or less)
    • chronic immunosuppression in the post-transplant setting, including organ transplant

See Attachment A for examples of disease settings and chemotherapy regimens with a high (>20%) or intermediate (10-20%) risk for febrile neutropenia (Note: These are not all-inclusive lists)
  • Prophylaxis of chemotherapy-induced febrile neutropenia in individuals receiving nonmyelosuppressive chemotherapy who are considered to be at high risk for chemotherapy-induced febrile neutropenia infectious complications because of bone marrow compromise or comorbidity, including, but not limited to any of the following factors:
    • age greater than 65 years
    • poor performance status (Eastern Cooperative Oncology Group [ECOG] Performance Status 3-4)
    • previous episodes of febrile neutropenia
    • extensive prior treatment including large radiation ports
    • administration of combined chemoradiotherapy
    • bone marrow involvement by tumor producing cytopenias
    • poor nutritional status (baseline serum albumin 3.5 g/dL or less)
    • open wounds or active infections
    • more advanced cancer
  • Prophylaxis of chemotherapy-induced febrile neutropenia in individuals with one of the following indications, regardless of risk status:
    • Acute lymphocytic leukemia (ALL) after the completion of the initial first few days of chemotherapy of the initial induction or first postremission course
    • Acute myeloid leukemia (AML) who are septic and have a life-threatening infection, when receiving induction chemotherapy
    • Diffuse aggressive lymphoma in individuals age 65 years and older treated with curative chemotherapy regimen cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP)
    • In pediatric individuals where dose-intense chemotherapy is administered for an indication that is known to have a survival benefit (e.g., Ewing sarcoma)
    • Dose-dense therapy (standard doses given more frequently) for the adjuvant treatment of high-risk breast cancer or for use of high-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-MVAC) in urothelial cancer
  • Secondary prophylaxis in individuals who have experienced a neutropenic event from a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose or treatment delay may compromise disease-free or overall survival or treatment outcome
  • Therapeutic use in individuals with cancer who have fever and neutropenia and are at high risk for infection-associated complications or who have prognostic factors that are predictive of poor clinical outcomes. High-risk features include the following factors:
    • expected prolonged (greater than 10 days) and profound (less than 0.1 X 109/L) neutropenia
    • age greater than 65 years
    • uncontrolled primary disease
    • pneumonia
    • hypotension and multiorgan dysfunction (sepsis syndrome)
    • invasive fungal infection
    • hospitalization at the time of fever development
  • Intermittent use in individuals with myelodysplastic syndromes (MDS) who have severe neutropenia and recurrent infection
  • Therapeutic use after accidental or intentional total body radiation of myelosuppressive doses (greater than 2 Grays [Gy]), if prolonged delays secondary to neutropenia are expected
    • Use of the On-body Injector for Neulasta® (Neulasta® Onpro kit) has not been studied and is not recommended for this indication
  • Mobilization of peripheral blood progenitor cells prior to autologous transplantation in individuals with hematological malignancies, when used alone, after chemotherapy, or in combination with plerixafor
  • After autologous hematopoietic stem-cell transplant to reduce the duration of severe neutropenia

EXPERIMENTAL/INVESTIGATIONAL

All other uses for pegfilgrastim (Neulasta®) and related biosimilars are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

Pegfilgrastim (Neulasta®) and related biosimilars are available as a single-dose prefilled syringe for manual use only. Pegfilgrastim (Neulasta®) is also available as a single-dose prefilled syringe co-packed with the On-body Injector for Neulasta® (Neulasta® Onpro kit).

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, pegfilgrastim (Neulasta®) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

Pegfilgrastim (Neulasta®) and related biosimilars may be available under the applicable medical or pharmacy benefit. Individual benefits must be verified.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Pegfilgrastim (Neulasta®) was approved by the FDA on January 31, 2002 to decrease the incidence of infection, as manifested by febrile neutropenia, in individuals with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Supplemental approvals for pegfilgrastim (Neulasta®) have since been issued by the FDA. The FDA has also issued subsequent approvals for biosimilar products.

PEDIATRIC USE

The safety and effectiveness of pegfilgrastim (Neulasta®) and related biosimilars have been established in pediatric patients. Use of the On-body Injector for Neulasta® (Neulasta® Onpro kit) has not been studied in pediatric patients.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.

ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work)
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.


Description

Certain intensive cytotoxic chemotherapy regimens are known to cause severe, prolonged febrile neutropenia that may increase the risk of infections and hospitalization. The risk of febrile neutropenia is related to the treatment regimen and delivered dose intensity. The National Comprehensive Cancer Network (NCCN) defines febrile neutropenia as a single temperature of 38.3°C or greater orally, or 38.0°C over 1 hour; neutropenia as less than 500 neutrophils/mcL or less than 1,000 neutrophils/mcL and a predicted decline to 500 neutrophils/mcL or less over the next 48 hours.

Granulocyte colony-stimulating factor (G-CSF) has been shown to reduce the duration and severity of neutropenia, as well as the risk of febrile neutropenia, thereby enabling the delivery of the current dose of chemotherapy or even dose-intensive (increased dose) or dose-dense (increased frequency) regimens when indicated. Without the use of G-CSFs in some chemotherapy regimens, the need to reduce the chemotherapeutic dose may cause a poor prognosis for the individual.

Pegfilgrastim (Neulasta®) is a G-CSF that affects the proliferation and differentiation of neutrophils within the bone marrow. Pegfilgrastim (Neulasta®) was approved by the US Food and Drug Administration (FDA) in 2002 to decrease the incidence of infection, as manifested by febrile neutropenia, in individuals with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. A subsequent indication was FDA-approved to increase survival in individuals acutely exposed to myelosuppressive doses of radiation.

Since 2018, the FDA has approved several biosimilar products. These are highly similar to the reference biologic, pegfilgrastim (Neulasta®), and have the same indications; there are no clinically meaningful differences between the biosimilars and the reference product.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Aapro MS, Bohlius J, Cameron DA, et al; European Organisation for Research and Treatment of Cancer. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8-32. Epub 2010 Nov 20.

American Hospital Formulary Service (AHFS). Drug Info 2016. Pegfilgrastim (Neulasta®). [Lexicomp Online Web site]. 01/01/2009. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 04, 2019.

Coherus Biosciences. Udenyca: Dosing & Administration [Udenyca Web site]. Available at: https://udenyca.com/dosing-administration/. Accessed March 04, 2019.

Elsevier’s Gold Standard Clinical Pharmacology Compendium. Pegfilgrastim (Neulasta®). 05/16/16. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed March 04, 2019.

Lexi-Drugs Compendium. Pegfilgrastim (Neulasta®). 08/01/16. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 04, 2019.

Mylan Pharmaceuticals, Inc. Fulphila (pegfilgrastim-jmdb) package insert. 2018. Available at: http://www.fulphila.com/-/media/fulphilacom/pdf/peg_2018_0066_fulphilacondensedvisualaid.pdf?la=en . Accessed March 07, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Acute Lymphoblastic Leukemia. V1.2016. 04/06/16. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#all [via free subscription]. Accessed March 04, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Acute Myeloid Leukemia. V2.2016. 06/29/16. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#aml [via free subscription]. Accessed March 04, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Myelodysplastic Syndromes. V1.2017. 08/18/16. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#mds [via free subscription]. Accessed March 04, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Myeloid growth factors. V2.2016. 07/27/16. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#myeloid_growth [via free subscription]. Accessed March 04, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. pegfilgrastim (Neulasta®). [NCCN Web site]. 2016. Available at: https://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=52 [via subscription only]. Accessed March 04, 2019.

National Institutes of Health U.S. National Library of Medicine. FULPHILA- pegfilgrastim injection [DailyMed Web site]. Available at:https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ea915d7-2feb-4e75-91f7-913c965b7d8a. Accessed March 04, 2019.

Pegfilgrastim (Neulasta®). [prescribing information] Thousand Oaks, CA: Amgen Inc.; updated 04/2016. Available at: http://www.neulastahcp.com/ . Accessed March 04, 2019.

Smith TJ, Bohlke K, Lyman GH, et al; 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(28):3199-212. Epub 2015 Jul 13.

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):3187-205. Epub 2006 May 8.

Truven Health Analytics. Micromedex® DrugDex® Compendium. pegfilgrastim (Neulasta®). 08/12/16. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 04, 2019.

US Food and Drug Administration (FDA). Scientific considerations in demonstrating biosimilarity to a reference product: guidance for industry [FDA Web site]. Available at:https://www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Published April 2015. Accessed March 04, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. pegfilgrastim (Neulasta) drug label & approval letter [FDA Web site]. updated 04/2016. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm . Accessed March 04, 2019.

US Food and Drug Administration (FDA). Drugs@FDA: FDA Approved Drug Products. pegfilgrastim-bmez (Ziextenzo) drug label [FDA Web site]. updated 11/2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761045lbl.pdf . Accessed March 17, 2020.

US Food and Drug Administration (FDA). Drugs@FDA: FDA Approved Drug Products. pegfilgrastim-jmdb (Fulphila) drug label [FDA Web site]. updated 06/2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761075s000lbl.pdf Accessed March 01, 2019.

US Food and Drug Administration (FDA). Drugs@FDA: FDA Approved Drug Products. Pegfilgrastim-cbqv (Udenyca) drug label [FDA Web site]. updated 11/2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761039s000lbl.pdf. Accessed March 01, 2019.

US Food and Drug Administration (FDA). FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment [FDA Web site]. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm609805.htm. Published June 2018. Accessed March 04, 2019.

Vogel CL, Wojtukiewicz MZ, Carroll RR, et al. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol. 2005;23(6):1178-84.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

D70.1 Agranulocytosis secondary to cancer chemotherapy

D70.8 Other neutropenia

D70.9 Neutropenia, unspecified

D75.9 Disease of blood and blood-forming organs, unspecified

Z48.298 Encounter for aftercare following other organ transplant

Z52.011 Autologous donor, stem cells




HCPCS Level II Code Number(s)



THE FOLLOWING CODE IS USED TO REPRESENT PEGFILGRASTIM (NEULASTA®)
J2505 Injection, pegfilgrastim, 6 mg

THE FOLLOWING CODES ARE USED TO REPRESENT PEGFILGRASTIM-BMEZ (ZIEXTENZOTM)
C9058 Injection, pegfilgrastim-bmez, biosimilar, (ziextenzo) 0.5 mg
J3590 Unclassified biologics

THE FOLLOWING CODE IS USED TO REPRESENT PEGFILGRASTIM-CGQV (UDENYCA™)
Q5111 Injection, pegfilgrastim-cbqv, biosimilar, (Udenyca), 0.5 mg

THE FOLLOWING CODE IS USED TO REPRESENT PEGFILGRASTIM-JMDB (FULPHILA®)
Q5108 Injection, pegfilgrastim-jmdb, biosimilar, (Fulphila), 0.5 mg



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Pegfilgrastim (Neulasta®) and Related Biosimilars
Description: EXAMPLES OF DISEASE SETTINGS AND CHEMOTHERAPY REGIMENS WITH A HIGH (>20%) OR INTERMEDIATE (10-20%) RISK FOR FEBRILE NEUTROPENIA




Policy History

08.01.32b
04/01/2020This policy has been identified for the HCPCS code update, effective 04/01/2020.

The following HCPCS codes have been added to this policy:
THE FOLLOWING CODES ARE USED TO REPRESENT PEGFILGRASTIM-BMEZ (ZIEXTENZOTM)
C9058 Injection, pegfilgrastim-bmez, biosimilar, (ziextenzo) 0.5 mg
J3590 Unclassified biologics

08.01.32a
04/22/2019This version of the policy will become effective 04/22/2019.

This policy has been updated to communicate continuing coverage for pegfilgrastim (Neulasta®), and to expand coverage to biosimilar drugs in light of recent approvals from the US Food and Drug Administration (FDA) for pegfilgrastim-cbqv (Udenyca™) and pegfilgrastim-jmdb (Fulphila™). The following ICD-10 code was added to the policy: D75.9. The following HCPCS codes have been added to this policy: Q5108, Q5111.

08.01.32
11/22/2017This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.
Version Effective Date: 04/01/2020
Version Issued Date: 04/03/2020
Version Reissued Date: N/A

Connect with Us        


© 2017 Independence Blue Cross.
Independence Blue Cross is an independent licensee of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.