Pegfilgrastim (Neulasta®); Pegfilgrastim-jmdb (Fulphila®); Pegfilgrastim--pbbk (Fylnetra®); Pegfilgrastim- apgf (Nyvepria™); Pegfilgrastim-fpgk (Stimufed®); Pegfilgrastim-cbqv (Udenyca®); Pegfilgrastim-bmez (Ziextenzo™)
Some agents on this policy may require step therapy See “Step Therapy Requirements for Provider Administered Specialty Medications” Document at: https://www.bcbst.com/docs/providers/Comm_BC_PAD_Step_Therapy_Guide.pdf
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 or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
POLICY
I. INDICATIONS
The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.
A. FDA-Approved Indication
Neulasta
1. Patients with Cancer Receiving Myelosuppressive Chemotherapy
Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
2. Hematopoietic Subsyndrome of Acute Radiation Syndrome
Neulasta is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome).
Fulphila
Patients with Cancer Receiving Myelosuppressive Chemotherapy
Fulphila is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia
Udenyca
1. Patients with Cancer Receiving Myelosuppressive Chemotherapy
Udenyca is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
2. Hematopoietic Subsyndrome of Acute Radiation Syndrome
Udenyca is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.
Ziextenzo
Patients with Cancer Receiving Myelosuppressive Chemotherapy
Ziextenzo is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Nyvepria
Patients with Cancer Receiving Myelosuppressive Chemotherapy
Nyvepria is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Fylnetra
Patients with Cancer Receiving Myelosuppressive Chemotherapy
Fylnetra is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Stimufend
Patients with Cancer Receiving Myelosuppressive Chemotherapy
Stimufend is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
B. Compendial Use
1. Stem cell transplantation-related indications
2. Prophylaxis for chemotherapy-induced febrile neutropenia in patients with solid tumors
3. Hematopoietic Subsyndrome of Acute Radiation Syndrome
4. Hairy cell leukemia, neutropenic fever
All other indications are considered experimental/investigational and not medically necessary.
II. DOCUMENTATION
Primary Prophylaxis of Febrile Neutropenia
A. Documentation must be provided of the member’s diagnosis and chemotherapeutic regimen.
B. If chemotherapeutic regimen has a low or intermediate risk of febrile neutropenia (less than 20%), documentation must be provided outlining the member’s risk factors that confirm the member is at high risk for febrile neutropenia.
III. CRITERIA FOR INITIAL APPROVAL
A. Prevention of neutropenia in cancer patients receiving myelosuppressive chemotherapy
Authorization of 6 months may be granted for prevention of febrile neutropenia when all of the following criteria are met (1, 2, 3, and 4):
1. The requested medication will not be used in combination with other colony stimulating factors within any chemotherapy cycle.
2. The member will not receive chemotherapy at the same time they receive radiation therapy.
3. The requested medication will not be administered with weekly chemotherapy regimens.
4. One of the following criteria is met (i or ii):
i. The requested medication will be used for primary prophylaxis in members with a solid tumor or non-myeloid malignancies who have received, are currently receiving, or will be receiving any of the following;
a) Myelosuppressive anti-cancer therapy that is expected to result in 20% or higher incidence of febrile neutropenia (FN) (See Appendix A)
b) Myelosuppressive anti-cancer therapy that is expected to result in 10 – 19% risk of FN (See Appendix B) and who are considered to be at high risk of FN because of bone marrow compromise or co- morbidities, or other patient specific risk factors (See Appendix C).
c) Myelosuppressive anti-cancer therapy that is expected to result in less than 10% risk of FN and who have at least 2 patient-related risk factors (See Appendix C).
ii. The requested medication will be used for secondary prophylaxis in members with solid tumors or non-myeloid malignancies who experienced a febrile neutropenic complication or a dose-limiting neutropenic event (a nadir or day of treatment count impacting the planned dose of chemotherapy) from a prior cycle of similar chemotherapy, with the same dose and scheduled planned for the current cycle (for which primary prophylaxis was not received).
B. Other indications
Authorization of 6 months may be granted for members with any of the following indications:
1. Stem cell transplantation-related indications
2. Hematopoietic Subsyndrome of Acute Radiation Syndrome
Treatment for radiation-induced myelosuppression following a radiological/nuclear incident
3. Hairy cell leukemia
Members with hairy cell leukemia with neutropenic fever following chemotherapy
IV. CONTINUATION OF THERAPY
All members (including new members) requesting authorization for continuation of therapy must meet all initial authorization criteria.
V. APPENDIX
A. APPENDIX A: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 20% or Higher*†
1. Acute Lymphoblastic Leukemia:
Select ALL regimens as directed by treatment protocol (see NCCN guidelines ALL)
2. Bladder Cancer:
i. Dose dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)
ii. CBDCa/Pac (carboplatin, paclitaxel)
3. Bone Cancer
i. VAI (vincristine, doxorubicin or dactinomycin, ifosfamide)
ii. VDC-IE (vincristine, doxorubicin or dactinomycin, and cyclophosphamide alternating with ifosfamide and etoposide)
iii. Cisplatin/doxorubicin
iv. VDC (cyclophosphamide, vincristine, doxorubicin or dactinomycin)
v. VIDE (vincristine, ifosfamide, doxorubicin or dactinomycin, etoposide)
4. Breast Cancer:
i. Docetaxel + trastuzumab
ii. Dose-dense AC (doxorubicin, cyclophosphamide) + paclitaxel (or dose dense paclitaxel)
iii. TAC (docetaxel, doxorubicin, cyclophosphamide)
iv. AT (doxorubicin, docetaxel)
v. Doc (docetaxel)
vi. TC (docetaxel, cyclophosphamide)
vii. TCH (docetaxel, carboplatin, trastuzumab)
5. Colorectal Cancer:
FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan)
6. Esophageal and Gastric Cancers:
Docetaxel/cisplatin/fluorouracil
7. Head and Neck Squamous Cell Carcinoma
TPF (docetaxel, cisplatin, 5-fluorouracil)
8. Hodgkin Lymphoma:
i. Brentuximab vedotin + AVD (doxorubicin, vinblastine, dacarbazine)
ii. Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
9. Kidney Cancer:
Doxorubicin/gemcitabine
10. Non-Hodgkin's Lymphoma:
i. CHP (cyclophosphamide, doxorubicin, prednisone) + brentuximab vedotin
ii. Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)
iii. ICE (ifosfamide, carboplatin, etoposide)
iv. Dose-dense CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone) ± rituximab
v. MINE (mesna, ifosfamide, mitoxantrone, etoposide)
vi. DHAP (dexamethasone, cisplatin, cytarabine)
vii. ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine (Ara-C))
viii. HyperCVAD ± rituximab (cyclophosphamide, vincristine, doxorubicin, dexamethasone ± rituximab)
ix. VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide, bleomycin)
11. Melanoma:
Dacarbazine-based combination with IL-2, interferon alpha (dacarbazine, cisplatin, vinblastine, IL-2, interferon alfa)
12. Multiple Myeloma:
i. VTD-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide + bortezomib)
ii. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide)
13. Ovarian Cancer:
i. Topotecan
ii. Docetaxel
14. Soft Tissue Sarcoma:
i. MAID (mesna, doxorubicin, ifosfamide, dacarbazine)
ii. Doxorubicin
iii. Ifosfamide/doxorubicin
15. Small Cell Lung Cancer:
i. Top (topotecan)
ii. CAV (cyclophosphamide, doxorubicin, vincristine)
16. Testicular Cancer:
i. VelP (vinblastine, ifosfamide, cisplatin)
ii. VIP (etoposide, ifosfamide, cisplatin)
iii. TIP (paclitaxel, ifosfamide, cisplatin)
17. Gestational Trophoblastic Neoplasia:
i. EMA/CO (etoposide, methotrexate, dactinomycin/cyclophosphamide, vincristine)
ii. EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin)
iii. EP/EMA (etoposide, cisplatin/etoposide, methotrexate, dactinomycin)
iv. TP/TE (paclitaxel, cisplatin/paclitaxel, etoposide)
v. BEP (bleomycin, etoposide, cisplatin)
vi. VIP (etoposide, ifosfamide, cisplatin)
vii. ICE (ifosfamide, carboplatin, etoposide)
18. Wilms Tumor:
i. Regimen M (vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide)
ii. Regimen I (vincristine, doxorubicin, cyclophosphamide, etoposide)
*Applies to chemotherapy regimens with or without monoclonal antibodies (e.g., trastuzumab, rituximab)
† This list is not comprehensive; there are other agents/regimens that have an intermediate/high risk for development of febrile neutropenia.
B. APPENDIX B: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 10% to 19%*†
1. Occult Primary – Adenocarcinoma:
Gemcitabine/docetaxel
2. Breast Cancer:
i. Docetaxel
ii. CMF classic (cyclophosphamide, methotrexate, fluorouracil)
iii. CA (doxorubicin, cyclophosphamide) (60 mg/m2) (hospitalized)
iv. AC (doxorubicin, cyclophosphamide) + sequential docetaxel (taxane portion only)
v. AC + sequential docetaxel + trastuzumab
vi. A (doxorubicin) (75 mg/m2)
vii. AC (doxorubicin, cyclophosphamide)
viii. CapDoc (capecitabine, docetaxel)
ix. Paclitaxel every 21 days
3. Cervical Cancer:
i. Irinotecan
ii. Cisplatin/topotecan
iii. Paclitaxel/cisplatin
iv. Topotecan
4. Colorectal Cancer:
i. FL (fluorouracil, leucovorin)
ii. CPT-11 (irinotecan) (350 mg/m2 q 3 wk)
iii. FOLFOX (fluorouracil, leucovorin, oxaliplatin)
iv. FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, irinotecan)
5. Esophageal and Gastric Cancers:
i. Irinotecan/cisplatin
ii. Epirubicin/cisplatin/5-fluorouracil
iii. Epirubicin/cisplatin/capecitabine
6. Non-Hodgkin's Lymphomas:
i. EPOCH-IT chemotherapy
ii. GDP (gemcitabine, dexamethasone, cisplatin/carboplatin)
iii. GDP (gemcitabine, dexamethasone, cisplatin/carboplatin) + rituximab
iv. FMR (fludarabine, mitoxantrone, rituximab)
v. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) including regimens with pegylated liposomal doxorubicin
vi. CHOP + rituximab (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) including regimens with pegylated liposomal doxorubicin
vii. Bendamustine
7. Non-Small Cell Lung Cancer:
i. Cisplatin/paclitaxel
ii. Cisplatin/vinorelbine
iii. Cisplatin/docetaxel
iv. Cisplatin/etoposide
v. Carboplatin/paclitaxel
vi. Docetaxel
8. Ovarian Cancer:
Carboplatin/docetaxel
9. Pancreatic Cancer:
FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, irinotecan)
10. Prostate Cancer:
Cabazitaxel
11. Small Cell Lung Cancer:
Etoposide/carboplatin
12. Testicular Cancer:
i. BEP (bleomycin, etoposide, cisplatin)
ii. Etoposide/cisplatin
13. Uterine Sarcoma:
Docetaxel
*Applies to chemotherapy regimens with or without monoclonal antibodies (e.g., trastuzumab, rituximab)
† This list is not comprehensive; there are other agents/regimens that have an intermediate/high risk for development of febrile neutropenia.
C. APPENDIX C: Patient Risk Factors*
1. Active infections, open wounds, or recent surgery
2. Age greater than or equal to 65 years
3. Bone marrow involvement by tumor producing cytopenias
4. Previous chemotherapy or radiation therapy
5. Poor nutritional status
6. Poor performance status
7. Previous episodes of FN
8. Other serious co-morbidities, including renal dysfunction, liver dysfunction, HIV infection, cardiovascular disease
9. Persistent neutropenia
*This list is not all-inclusive.
MEDICATION QUANTITY LIMITS
Drug Name |
Diagnosis |
Maximum Dosing Regimen |
Neulasta (Pegfilgrastim) Udenyca (Pegfilgrastim-cbqv) |
Hematopoietic Subsyndrome of Acute Radiation Syndrome |
Route of Administration: Subcutaneous ≥18 Years 6mg every week for 2 doses
≤17 Years <10kg: 0.1mg/kg every week for 2 doses 10-20kg: 1.5mg every week for 2 doses 21-30kg: 2.5mg every week for 2 doses 31-44kg: 4mg every week for 2 doses ≥45kg: 6mg every week for 2 doses |
Fulphila Fylnetra Nyvepria (Pegfilgrastim-apgf) Stimufend (Pegfilgrastim-fpgk) Ziextenzo (Pegfilgrastim-bmez) |
Hematopoietic Subsyndrome of Acute Radiation Syndrome |
Route of Administration: Subcutaneous ≥ 18 Years 6mg every week for 2 doses
<18 Years <10kg: 0.1mg/kg every week for 2 doses > 10kg to <21kg: 1.5mg every week for 2 doses > 21kg to < 31kg: 2.5mg every week for 2 doses > 31kg to <45kg: 4mg every week for 2 doses > 45kg: 6mg every week for 2 doses |
Neulasta (Pegfilgrastim) Ziextenzo (Pegfilgrastim-bmez)
|
Prevention of Febrile Neutropenia |
Route of Administration: Subcutaneous ≤18 Years <10kg 0.1mg/kg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
10-20kg 1.5mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
21-30kg 2.5mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
31-44kg 4mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
≥45kg 6mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
≥18 Years 6mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy |
Fulphila (Pegfilgrastim-jmdb) Fylnetra (Pegfilgrastim-pbbk) Nyvepria (Pegfilgrastim-apgf) Stimufed (Pegfilgrastim-fpgk) Udenyca (Pegfilgrastim-cbqv)
|
Prevention of Febrile Neutropenia |
Route of Administration: Subcutaneous ≤17 Years <10kg 0.1mg/kg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
10-20kg 1.5mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
21-30kg 2.5mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
31-44kg 4mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
≥45kg 6mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy
≥18 Years 6mg once per chemotherapy cycle; do not administer between 14 days prior to and 24 hours after administration of chemotherapy |
Neulasta (Pegfilgrastim) Fulphila (Pegfilgrastim-jmdb) Fylnetra (Pegfilgrastim-pbbk) Nyvepria (Pegfilgrastim-apgf) Stimufed (Pegfilgrastim-fpgk) Udenyca (Pegfilgrastim-cbqv) Ziextenzo (Pegfilgrastim-bmez)
|
Stem Cell Transplantation-Related Indications |
Route of Administration: Subcutaneous 6mg once |
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
ADDITIONAL INFORMATION
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
REFERENCES
1. Neulasta [package insert]. Thousand Oaks, CA: Amgen Inc.; February 2021.
2. Fulphila [package insert]. Morgantown, WV: Mylan Pharmaceuticals, Inc.; October 2021.
3. Udenyca [package insert]. Redwood City, CA: Coherus BioSciences, Inc.; March 2023.
4. Ziextenzo [package insert]. Princeton, NJ: Sandoz Inc.; March 2021.
5. Nyvepria [package insert]. Lake Forest, IL: Hospira, Inc.; March 2023.
6. Fylnetra [package insert]. Piscataway, NJ: Kashiv BioSciences, LLC; May 2022.
7. Stimufend [package insert]. Lake Zurich, IL: Fresenius Kabi USA, LLC; September 2022.
8. The NCCN Drugs & Biologics Compendium® © 2023 National Comprehensive Cancer Network, Inc. Available at: https://www.nccn.org Accessed June 20, 2023.
9. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Growth Factors. Version 2.2023. https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf Accessed June 13, 2023.
10. IBM Micromedex® DRUGDEX ® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at https://www.micromedexsolutions.com (Accessed: June 20, 2023)
11. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of white blood cell growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28):3199-3212.
12. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia. Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/hairy_cell.pdf Accessed June 19, 2023.
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):3187-3205.
14. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Gestational Trophoblastic Neoplasia. Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/gtn.pdf Accessed June 19, 2023.
15. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Wilms Tumor (Nephroblastoma). Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/wilms_tumor.pdf Accessed June 19, 2023.
ORIGINAL EFFECTIVE DATE: 12/1/2016
MOST RECENT REVIEW DATE: 4/30/2024
ID_CHS
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.
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