Requires 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

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.

FDA-Approved Indications

Ryzneuta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Compendial Uses

Stem cell transplantation-related indications
Prophylaxis for chemotherapy-induced febrile neutropenia in patients with solid tumors
Hematopoietic acute radiation syndrome
Hairy cell leukemia, neutropenic fever

DOCUMENTATION

Primary Prophylaxis of Febrile Neutropenia

Documentation must be provided of the member’s diagnosis and chemotherapeutic regimen.
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.

COVERAGE CRITERIA

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:

The requested medication will not be used in combination with other colony stimulating factors within any chemotherapy cycle.
The member will not receive chemotherapy at the same time as they receive radiation therapy.
The requested medication will not be administered with weekly chemotherapy regimens.
One of the following criteria is met:

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:

Myelosuppressive anti-cancer therapy that is expected to result in 20% or higher incidence of febrile neutropenia (FN) (See Appendix A).
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, co-morbidities, or other patient specific risk factors (See Appendix 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).

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).

Other Indications

Authorization of 6 months may be granted for members with any of the following indications:

Stem cell transplantation-related indications
Hematopoietic Acute Radiation Syndrome
Treatment for radiation-induced myelosuppression following a radiological/nuclear incident
Hairy cell leukemia
Members with hairy cell leukemia with neutropenic fever following chemotherapy

CONTINUATION OF THERAPY

All members (including new members) requesting authorization for continuation of therapy must meet all requirements in the coverage criteria.

APPENDIX

Appendix A: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 20% or Higher

This list is not comprehensive; there are other agents/regimens that have an intermediate/high risk for development of febrile neutropenia.

Acute Lymphoblastic Leukemia

Select ALL regimens as directed by treatment protocol (see NCCN guidelines ALL)

Bladder Cancer

Dose dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)

Bone Cancer

VAIA (vincristine, doxorubicin, ifosfamide, and dactinomycin)
VDC-IE (vincristine, doxorubicin or dactinomycin, and cyclophosphamide alternating with ifosfamide and etoposide)
Cisplatin/doxorubicin
VDC (cyclophosphamide, vincristine, doxorubicin or dactinomycin)
VIDE (vincristine, ifosfamide, doxorubicin or dactinomycin, etoposide)

Breast Cancer

Dose-dense AC (doxorubicin, cyclophosphamide) followed by dose-dense paclitaxel
TAC (docetaxel, doxorubicin, cyclophosphamide)
TC (docetaxel, cyclophosphamide)
TCH (docetaxel, carboplatin, trastuzumab)

Head and Neck Squamous Cell Carcinoma

TPF (docetaxel, cisplatin, 5-fluorouracil)

Hodgkin Lymphoma

Brentuximab vedotin + AVD (doxorubicin, vinblastine, dacarbazine)
Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)

Kidney Cancer

Doxorubicin/gemcitabine

Non-Hodgkin's Lymphoma

CHP (cyclophosphamide, doxorubicin, prednisone) + brentuximab vedotin
Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) ± rituximab
ICE (ifosfamide, carboplatin, etoposide) ± rituximab
Dose-dense CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone) ± rituximab
MINE (mesna, ifosfamide, mitoxantrone, etoposide) ± rituximab
DHAP (dexamethasone, cisplatin, cytarabine) ± rituximab
ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine) ± rituximab
HyperCVAD ± rituximab (cyclophosphamide, vincristine, doxorubicin, dexamethasone ± rituximab)
Pola-R-CHP (polatuzumab vedotin-piiq, rituximab, cyclophosphamide, doxorubicin, prednisone)

Melanoma

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

Multiple Myeloma

VTD-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide + bortezomib)
DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide)

Ovarian Cancer

Topotecan ± bevacizumab
Docetaxel

Soft Tissue Sarcoma

MAID (mesna, doxorubicin, ifosfamide, dacarbazine)
Doxorubicin
Ifosfamide/doxorubicin

Small Cell Lung Cancer

Topotecan

Testicular Cancer

VelP (vinblastine, ifosfamide, cisplatin)
VIP (etoposide, ifosfamide, cisplatin)
TIP (paclitaxel, ifosfamide, cisplatin)

Gestational Trophoblastic Neoplasia

EMA/CO (etoposide, methotrexate, dactinomycin/cyclophosphamide, vincristine)
EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin)
EP/EMA (etoposide, cisplatin/etoposide, methotrexate, dactinomycin)
TP/TE (paclitaxel, cisplatin/paclitaxel, etoposide)
BEP (bleomycin, etoposide, cisplatin)
VIP (etoposide, ifosfamide, cisplatin)
ICE (ifosfamide, carboplatin, etoposide)

Wilms Tumor

Regimen M (vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide)
Regimen I (vincristine, doxorubicin, cyclophosphamide, etoposide)

Applies to chemotherapy regimens with or without monoclonal antibodies (e.g., trastuzumab, rituximab)

Appendix B: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 10% to 19%

This list is not comprehensive; there are other agents/regimens that have an intermediate/high risk for development of febrile neutropenia.

Occult Primary – Adenocarcinoma

Gemcitabine/docetaxel

Breast Cancer

Docetaxel ± trastuzumab
AC (doxorubicin, cyclophosphamide) + sequential docetaxel (taxane portion only)
AC + sequential docetaxel + trastuzumab
Paclitaxel every 21 days ± trastuzumab
TC (docetaxel, cyclophosphamide)

Cervical Cancer

Irinotecan
Cisplatin/topotecan
Paclitaxel/cisplatin ± bevacizumab
Topotecan

Colorectal Cancer

FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, irinotecan)

Esophageal and Gastric Cancers

Irinotecan/cisplatin

Non-Hodgkin's Lymphomas

GDP (gemcitabine, dexamethasone, cisplatin/carboplatin)
GDP (gemcitabine, dexamethasone, cisplatin/carboplatin) + rituximab
CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) including regimens with pegylated liposomal doxorubicin
CHOP + rituximab (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) including regimens with pegylated liposomal doxorubicin
Bendamustine

Non-Small Cell Lung Cancer

Cisplatin/paclitaxel
Cisplatin/vinorelbine
Cisplatin/docetaxel
Cisplatin/etoposide
Carboplatin/paclitaxel
Docetaxel

Ovarian Cancer

Carboplatin/docetaxel

Pancreatic Cancer

FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, irinotecan)

Prostate Cancer

Cabazitaxel

Small Cell Lung Cancer

Etoposide/carboplatin

Testicular Cancer

BEP (bleomycin, etoposide, cisplatin)
Etoposide/cisplatin

Uterine Sarcoma

Docetaxel

Applies to chemotherapy regimens with or without monoclonal antibodies (e.g., trastuzumab, rituximab)

Appendix C: Patient Risk Factors

This list is not all-inclusive.

Active infections, open wounds, or recent surgery
Age greater than or equal to 65 years
Bone marrow involvement by tumor producing cytopenias
Previous chemotherapy or radiation therapy
Poor nutritional status
Poor performance status
Previous episodes of FN
Other serious co-morbidities, including renal dysfunction, liver dysfunction, HIV infection, cardiovascular disease
Persistent neutropenia

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

Ryzneuta [package insert]. Singapore: Evive Biotechnology PTE. LTD.; November 2023.
The NCCN Drugs & Biologics Compendium® © 2024 National Comprehensive Cancer Network, Inc. Available at: https://www.nccn.org. Accessed June 5, 2024
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Growth Factors. Version 3.2024. https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf. Accessed June 6, 2024.
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.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation. Version 1.2024. https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf. Accessed June 6, 2024.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia. Version 2.2024. https://www.nccn.org/professionals/physician_gls/pdf/hairy_cell.pdf. Accessed June 6, 2024.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Gestational Trophoblastic Neoplasia. Version 1.2024. https://www.nccn.org/professionals/physician_gls/pdf/gtn.pdf. Accessed June 6, 2024.
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 6, 2024.

ORIGINAL EFFECTIVE DATE: 12/31/2025

MOST RECENT REVIEW DATE: 12/31/2025

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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