CurrentCareSourcePolicy N/A

Colony Stimulating Factors — Ryzneuta (efbemalenograstim) Utilization Management Medical Policy

Defines prior authorization requirements, coverage criteria, dosing, limitations, and exclusions for Ryzneuta (efbemalenograstim) for adults with non-myeloid malignancies receiving myelosuppressive chemotherapy. Applies to CareSource medical benefit reviews for members in North Carolina.

Policy Summary

PayerCareSource

PolicyColony Stimulating Factors — Ryzneuta (efbemalenograstim) Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeMaterial clinical updates & clarifications

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization with documentation that patient meets age, regimen FN risk, and risk-factor or prior neutropenic complication criteria; approvals granted for 6 months when criteria met.

SourceLink

POLICY UPDATE CHANGES

Examples of risk factors for febrile neutropenia were updated to age ≥65 years receiving full chemotherapy dose intensity and clarified laboratory thresholds for liver and renal dysfunction.

Requirement for prior neutropenic complication changed wording from 'previous' chemotherapy cycle to 'prior' chemotherapy cycle.

Policy explicitly states Ryzneuta is not indicated for PBPC mobilization for stem cell transplantation.

6 monthsinitial approval duration

>=20%auto-approval FN risk

10-20%intermediate FN risk

age >65example risk factor

bilirubin >2.0 mg/dLliver dysfunction threshold

Coverage Criteria for Ryzneuta (efbemalenograstim)

Initial FDA-Approved Indication

Covered when ALL of the following are met

FDA-Approved Indication Criteria: A) Patient is >= 18 years of age; AND B) Patient meets ONE of the following: (i) patient is receiving myelosuppressive anti-cancer medications associated with a high risk (>= 20%) of febrile neutropenia based on the chemotherapy regimen; OR (ii) patient is receiving myelosuppressive anti-cancer medications with regimen risk <20% AND meets BOTH of the following: (a) patient has had a neutropenic complication from a prior chemotherapy cycle and did not receive prophylaxis with a colony stimulating factor; AND (b) the prescriber identifies >=1 risk factor for febrile neutropenia (examples: age >65 years receiving full chemotherapy dose intensity; persistent neutropenia; bone marrow involvement by tumor; recent surgery or open wounds; liver dysfunction (bilirubin >2.0 mg/dL); renal dysfunction (creatinine clearance <= 50 mL/min); poor performance status; HIV with low CD4 count).see node text

Approval duration: 6 months; dosing: approve 20 mg SC no more frequently than once every 2 weeks.

Ryzneuta is explicitly not indicated for mobilization of peripheral blood progenitor cells (PBPCs) for hematopoietic stem cell transplantation. The policy lists PBPC mobilization as a limitation of use and states that coverage is not recommended for this indication.

Policy Summary

PayerCareSource

PolicyColony Stimulating Factors — Ryzneuta (efbemalenograstim) Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeMaterial clinical updates & clarifications

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Use of Ryzneuta for PBPC collection and therapy is stated as not recommended and considered not medically necessary for that indication; requests for PBPC mobilization should be denied per the policy.

Coding and Risk Thresholds

Placeholder – no explicit codes listed in policy documentmixed

J3490

Not specified in document — provider should map as appropriate

Chemotherapy regimen febrile neutropenia risk

Routine prophylaxis threshold>= 20% regimen risk of febrile neutropenia for routine CSF prophylaxis

Consideration range10–20% regimen risk: CSF may be considered when additional patient-specific risk factors are present

Required documentation when regimen risk <20%Prescriber must document at least one FN risk factor or a prior neutropenic complication to support use

Approval duration when criteria metApprove for 6 months if all criteria are satisfied

Dosing limit noted in policyApprove 20 mg subcutaneous no more frequently than once every 2 weeks

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for medical benefit coverage of Ryzneuta. Approval is recommended for members who meet the required criteria below. Approvals will be granted for the duration specified in the clinical criteria (see criteria for initial approval duration). Requests for doses outside the dosing described in this policy will be reviewed on a case-by-case basis by a clinician (Medical Director or Pharmacist). Because of the specialized skills required for evaluation, diagnosis, and monitoring, Ryzneuta must be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., oncologist or hematologist).

Automation: None
Approvals: Approve for 6 months if ALL criteria are met (see FDA‑Approved Indication criteria)
Prescriber requirement: Prescribed by or in consultation with an oncologist or hematologist

Documentation Required

Required Documentation for Prior Authorization

Required documentation must be submitted with the prior authorization request to support approval. Clinical documentation should clearly demonstrate the member meets age and indication requirements, the specific chemotherapy regimen and its febrile neutropenia (FN) risk, prior neutropenic complications when applicable, prescriber specialty, and the requested dosing and administration schedule.

Member age (must be ≥ 18 years for the FDA‑approved cancer indication)
Diagnosis and indication for Ryzneuta
Chemotherapy regimen name and documented FN risk (≥20% or <20% with supporting risk factors)
If applicable, documentation of prior neutropenic complication(s) (e.g., febrile neutropenia, neutropenic sepsis) and whether prophylactic colony stimulating factor was used in prior cycles
Documentation of risk factors for FN when regimen FN risk is <20% (examples: age >65 receiving full dose intensity; persistent neutropenia; bone marrow involvement; recent surgery/open wounds; hepatic dysfunction with bilirubin >2 mg/dL; renal dysfunction with creatinine clearance ≤50 mL/min; poor performance status; HIV with low CD4 counts)
Statement that reduced dose or frequency of chemotherapy would compromise treatment outcome (when applicable)
Prescriber name, specialty (oncology/hematology), and contact information

Documentation Required

Prior Neutropenic Complication Consideration

When considering requests based on prior neutropenic complications (used when the patient’s chemotherapy regimen FN risk is <20%), the request must document the prior neutropenic event and the relationship to chemotherapy. Approval in this scenario requires evidence that the patient experienced a neutropenic complication in a prior chemotherapy cycle and that prophylactic colony stimulating factor was not used or was inadequate in that prior cycle. The prescriber must also document that reducing chemotherapy dose or frequency would likely compromise treatment outcomes and list the specific FN risk factors present.

Use this consideration only when regimen FN risk is <20%
Provide documentation of prior neutropenic complication(s) (e.g., febrile neutropenia) from a prior cycle
Document whether prophylactic colony stimulating factors (e.g., filgrastim, pegfilgrastim, eflapegrastim) were used in the prior cycle
Provide at least one prescriber‑identified FN risk factor when regimen FN risk is <20% (see examples in documentation requirements)
Prescriber must state that chemotherapy dose/frequency reduction would compromise treatment outcome

Denial Risk

Not Recommended Indications

Requests for indications not listed in the Recommended Authorization Criteria are not recommended for coverage. Specifically, coverage is not recommended for peripheral blood progenitor cell (PBPC) mobilization for hematopoietic stem cell transplantation, and other uses outside the listed criteria will be denied unless new published evidence supporting those uses is added to this policy.

Not recommended: PBPC collection and mobilization for stem cell transplantation
Not recommended: Any circumstance not listed in the Recommended Authorization Criteria

Background

Ryzneuta is a granulocyte colony stimulating factor (G-CSF) indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with non-myeloid malignancies receiving myelosuppressive anti-cancer therapy. The policy notes that Ryzneuta has a limitation of use and is not indicated for PBPC mobilization; safety and effectiveness in pediatric patients have not been established.

Definitions and Risk Categories

Febrile neutropenia (FN) risk categories

High FN risk≥ 20% incidence with a chemotherapy regimen

Intermediate FN risk10–20% where CSF may be considered based on additional patient risk factors

Examples of additional risk factorsage > 65 years, persistent neutropenia, bone marrow involvement, recent surgery/open wounds, bilirubin > 2.0 mg/dL, renal dysfunction (creatinine clearance noted in policy)

Line of Therapy

first-line

Prophylactic use context

Line of therapy context: Ryzneuta is indicated for prophylactic use with myelosuppressive chemotherapy regimens that carry specified febrile neutropenia (FN) risk; it has been studied for prophylaxis and not for treatment of established FN. Use is appropriate when the regimen FN risk meets criteria in the Initial FDA-Approved Indication.

Covered Regimens and Dosing

Regimen / Indication	Dosing	Coverage status
Prophylaxis to reduce the incidence of febrile neutropenia during myelosuppressive chemotherapy regimens with appropriate FN risk (high-risk regimens ≥20% FN) or for regimens with <20% FN when patient has prior neutropenic complication and reduced chemotherapy dose/frequency would compromise outcome	Approve 20 mg subcutaneous injection no more frequently than once every 2 weeks	Covered when ALL criteria met (age ≥18; regimen FN risk ≥20% OR regimen risk <20% plus required risk factors/prior neutropenic complication; prescribed by or in consultation with an oncologist/hematologist)