ModifiedUnitedHealthcarePolicy N/A

White Blood Cell Colony Stimulating Factors (for Indiana Only)

Medical benefit drug policy governing coverage and medical necessity criteria for white blood cell colony stimulating factors (long- and short-acting G-CSFs and GM-CSF) for UnitedHealthcare members in Indiana.

Policy Summary

PayerUnitedHealthcare

PolicyWhite Blood Cell Colony Stimulating Factors (for Indiana Only)

Policy CodePolicy N/A

Change TypeAdded product (Ryzneuta) and HCPCS code update (J9361)

Effective DateOct 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document febrile neutropenia risk assessment per InterQual and policy criteria when requesting CSF coverage.

SourceLink

POLICY UPDATE CHANGES

Revised list of applicable white blood cell colony stimulating factors (CSFs); added Ryzneuta (efbemalenograstim alfa-vuxw).

Added language indicating Ryzneuta is proven and medically necessary for hematopoietic syndrome of acute radiation syndrome, primary and secondary prophylaxis of chemotherapy-induced febrile neutropenia, and treatment of febrile neutropenia when criteria are met.

Added HCPCS code J9361 to applicable codes.

Updated Background, FDA, and References sections to reflect current information.

20+drug products referenced

J1442–J9361HCPCS codes listed

20%+primary prophylaxis threshold (FN risk)

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.

1new product added (Ryzneuta)

Coverage and Medical Necessity Criteria

Indication-specific medical necessity (examples — Nypozi, Rolvedon, Ryzneuta)

Covered when criteria specific to the drug and indication are met (examples below for Nypozi, Rolvedon, Ryzneuta and others).

Indications for Nypozi (filgrastim-txid)

BMT/PSCT mobilization: Patient has nonmyeloid malignancy AND is undergoing myeloablative chemotherapy followed by autologous or allogeneic bone marrow transplant OR patient had peripheral stem cell transplant and received myeloablative chemotherapy; agent is used for mobilization of hematopoietic progenitor cells into peripheral blood for leukapheresis.
Supports filgrastim use for mobilization per trials
AML induction/consolidation: Diagnosis of acute myeloid leukemia (AML) AND patient achieved complete remission after induction therapy OR patient is receiving consolidation chemotherapy OR patient is receiving specified regimens for relapsed/refractory disease (eg, cladribine; cytarabine ± mitoxantrone or idarubicin; fludarabine; cytarabine ± idarubicin); use consistent with trial evidence showing reduced duration of severe neutropenia.
Randomized trial evidence supports neutrophil recovery benefit
Primary prophylaxis of chemotherapy-induced FN: Patient is receiving dose-dense MVAC for bladder cancer OR dose-dense AC followed by dose-dense paclitaxel for breast cancer OR receiving chemotherapy regimens associated with ≥20% incidence of febrile neutropenia OR (if regimen incidence 10–20%) patient has one or more FN risk factors (eg, persistent neutropenia, renal or liver dysfunction, age >65, marrow involvement, prior chemo/radiation, recent surgery).
Per regimen- and patient-based risk assessment
Secondary prophylaxis of FN: Patient is receiving myelosuppressive anticancer drugs given with curative or definitive intent AND has documented history of a neutropenic event from prior chemotherapy OR experienced neutropenic event during previous cycle at full dose without prior prophylaxis OR had dose reduction trial followed by dose‑limiting neutropenic event causing delay; or patient receiving non‑curative intent chemotherapy with documented FN history; or use is consistent with FDA label.
ASCO-supported secondary prophylaxis scenarios
Treatment of FN (therapeutic use): Diagnosis of febrile neutropenia AND patient has one or more high‑risk features for infection‑associated complications such as no long‑acting pegfilgrastim in prior 14 days; sepsis syndrome; ANC <100/mcL; age >65; expected neutropenia >10 days; documented invasive infections including fungal pneumonia; hospitalization at time of fever; or prior episodes of FN.
Therapeutic CSF use reserved for high‑risk FN per guidance
Severe Chronic Neutropenia (SCN): Diagnosis of SCN (congenital, cyclic, or idiopathic) with chronic ANC <500 neutrophils/mcL AND prescribed by or in consultation with a hematologist/oncologist AND medication dosed per FDA labeling.
FDA‑aligned dosing and specialist involvement required
Hematopoietic syndrome of acute radiation syndrome: Patient has acute exposure to myelosuppressive doses of radiation AND agent is prescribed by or in consultation with a hematologist/oncologist AND medication is dosed in accordance with FDA approved labeling.
Animal efficacy data and regulatory indication support use

Indications supported by guidelines and evidence

Covered when meeting guideline- or evidence-based indications:

Primary prophylaxis: Patient has an anticipated risk of febrile neutropenia of approximately 20% or greater based on assessment of disease type, chemotherapy regimen (including dose‑dense or high‑dose), patient risk factors (age, organ dysfunction, marrow involvement, persistent neutropenia, prior chemo/radiation, recent surgery), and treatment intent; CSF is started with first chemotherapy cycle.FN risk >= ~20%

NCCN/ASCO recommendation

Secondary prophylaxis: Patient experienced a neutropenic complication from a prior chemotherapy cycle (without prior prophylaxis) and dose reduction or delay would compromise disease‑free or overall survival or treatment outcome; CSF use is considered to enable continued full‑dose therapy.prior neutropenic complication

ASCO recommendation

Febrile neutropenia treatment:

Indications considered medically necessary

Covered when criteria from guideline-aligned indications are met

Primary prophylaxis for chemotherapy-induced FN: Prophylactic G‑CSF is recommended when the overall risk of febrile neutropenia (FN) from the regimen and patient factors is >=20% or when dose‑dense/intense chemotherapy with survival benefit is used; consider patient‑related risk factors such as age ≥65 and comorbidities.overall FN risk >=20%

Based on ASCO and EORTC guidance

Secondary prophylaxis: Use of CSF for secondary prophylaxis (to prevent recurrent FN in subsequent cycles) is supported for patients with prior neutropenic complications per ASCO guidance.history of FN in prior cycle

ASCO recommendation

Treatment of FN: CSFs may be used therapeutically in patients with existing febrile neutropenia in special situations, such as failure to respond to appropriate antibiotics and development of life‑threatening infectious complications (e.g., severe sepsis or septic shock).

The inclusion of a procedure or diagnosis code in this policy is for reference only and does not imply that the service represented by the code is covered. Benefit coverage and reimbursement are determined by applicable federal, state, and contractual requirements and laws; other policies, guidelines, and claim submission rules may apply and can affect payment.

ASCO guidance states that routine use of colony stimulating factors (CSFs) as adjunctive therapy with antibiotics for patients who have fever and neutropenia is not recommended. CSFs may be considered only for patients with FN who are at high risk for infection-associated complications or who have prognostic factors predictive of poor outcomes; they are not indicated as routine adjunctive therapy for all FN patients.

ASCO recommends that the use of CSFs in pediatric patients is guided by clinical protocols. Specifically, CSFs should not be used in pediatric patients with non‑relapsed acute lymphoblastic leukemia (ALL) or non‑relapsed acute myeloid leukemia (AML) who do not have infection, and primary or secondary prophylaxis in children is reasonable only when the likelihood of febrile neutropenia is high or when dose‑intense regimens with demonstrated survival benefit require CSF support.

Coverage of requests for CSFs is contingent on meeting the policy's clinical criteria, which reference InterQual for drug‑specific medical necessity determinations. Prior authorization decisions rely on InterQual criteria and the diagnosis‑specific conditions in this policy; documentation should support that those criteria are met prior to approval.

ASCO explicitly advises that CSFs should not be used in pediatric patients with non‑relapsed ALL or non‑relapsed AML who do not have infection. Use in pediatric populations is generally protocol‑driven and should be reserved for indications such as dose‑intense regimens with proven survival benefit or other high‑risk situations described in pediatric treatment guidelines.

Guideline recommendations limit therapeutic use of G‑CSF for ongoing febrile neutropenia to exceptional circumstances. The EORTC and ASCO indicate that G‑CSF for ongoing FN is appropriate only in special situations—for example, when a patient is not responding to appropriate antibiotic therapy and is developing life‑threatening infectious complications such as severe sepsis or septic shock. Routine use in patients who are clinically responding to antibiotics is not supported.

Applicable Codes and Coding Notes

Applicable HCPCS/Q codesHCPCS

J1442	microgram.
J1447	Injection; tbo-filgrastim, 1 microgram.
J1449	Injection, eflapegrastim-xnst; 0.1 mg.
J2506	Injection, pegfilgrastim, excludes biosimilar; 0.5 mg.
J2820	Injection, sargramostim (GM-CSF), 50 mcg.
J9361	Injection, efbemalenograstim alfa-vuxw, 0.5 mg.
Q5101	Injection, filgrastim-sndz, biosimilar; (Zarxio), mcg.
Q5108	Injection, pegfilgrastim-jmdb (Fulphila) ; biosimilar; 0.5 mg.
Q5110	Injection, filgrastim-aafi, biosimilar, (Nivestym) , microgram.
Q5111	Injection, pegfilgrastim-cbqv (Udenyca) , biosimilar; 0.5 mg.

1–10 of 16

1/2

Referenced agents (HCPCS/NDC-level identifiers not specified in this section)mixed

filgrastim	G-CSF agent referenced (brand/generic names and biosimilars) - used for FN prevention, mobilization, post-transplant, radiation syndrome
pegfilgrastim	Pegylated G-CSF referenced for FN prevention and radiation syndrome
tbo-filgrastim	G-CSF biosimilar referenced for prevention and mobilization
filgrastim-sndz	biosimilar filgrastim referenced
filgrastim-aafi	biosimilar filgrastim referenced
sargramostim	GM-CSF agent referenced for AML, mobilization, transplant, and radiation syndrome

Applicable HCPCS Codes (updated)HCPCS

J9361

HCPCS code added to applicable codes

Febrile neutropenia risk thresholds

High-risk threshold>20% overall risk of chemotherapy-associated febrile neutropenia (FN)

Intermediate-risk band10–20% overall risk of FN

Low-risk threshold<10% overall risk of FN

FN risk threshold for primary prophylaxis

Primary prophylaxis decision pointApproximately 20% or higher anticipated FN risk warrants primary CSF prophylaxis

Dose‑dense regimensPrimary CSF prophylaxis should be administered for dose‑dense chemotherapy when appropriate

Prior Authorization, Documentation, and Provider Responsibilities

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Prior authorization is required for many colony stimulating factor (CSF) products and indications. UnitedHealthcare may reference the InterQual criteria when making medical necessity decisions.

Applicable HCPCS/Q codes (including newly added J9361) must be submitted with authorization requests and claims.
Prior authorization is typically expected for CSF indications such as primary and secondary prophylaxis for chemotherapy-induced febrile neutropenia (FN), post-transplant support, and peripheral-blood progenitor cell mobilization.

Billing Rule

Code Inclusion Is Not a Guarantee of Payment

Inclusion of a code in this policy does not guarantee reimbursement. Benefit coverage and payment are determined by federal, state, or contractual requirements and applicable laws.

Clinical Background and Evidence Context

Neutropenia is an abnormally low neutrophil count that increases a patient’s risk of infection and is a common toxicity of myelosuppressive chemotherapy. Neutropenia is defined as an absolute neutrophil count (ANC) < 1,500 neutrophils/mcL, and severe neutropenia as ANC < 500 neutrophils/mcL. Febrile neutropenia (FN) is typically defined by a qualifying fever (for example, single oral temperature ≥ 38.3°C or sustained ≥ 38.0°C over 1 hour) in the setting of neutropenia (ANC ≤ 500 neutrophils/mcL or ANC ≤ 1,000 with predicted decline to < 500 within 48 hours). CSFs (G‑CSF and GM‑CSF) reduce the duration and severity of neutropenia and the risk of febrile neutropenia, and they enable delivery of dose‑dense or intensive chemotherapy regimens when clinically indicated.

Key Definitions and Terms

Febrile Neutropenia definition

Temperature criterionSingle oral temperature ≥ 38.3°C or ≥ 38.0°C sustained over 1 hour

ANC criterion (absolute)ANC ≤ 500 neutrophils/mcL

Predicted ANC declineOr ANC ≤ 1,000 neutrophils/mcL with predicted decline to < 500 neutrophils/mcL within 48 hours

Neutropenia / Severe Neutropenia

NeutropeniaANC < 1,500 neutrophils/mcL

Severe neutropeniaANC < 500 neutrophils/mcL

Clinical relevance

Line of Therapy Considerations

Varied — 1 top-level node

Primary prophylaxis: Use when chemotherapy regimen FN risk ≥20% or 10–20% with patient risk factors; indicated for curative intent or definitive therapy where FN prevention is required.FN risk >=20% (or 10–20% with risk factors)

Line‑of‑therapy: varied; supports primary prophylaxis at treatment initiation

first-line — 1 top-level node

Induction/consolidation AML: Use of G‑CSF or GM‑CSF to reduce duration of severe neutropenia following induction or consolidation chemotherapy is supported by randomized trials demonstrating shorter neutropenia, reduced antibiotic use, and shorter hospitalizations.post‑chemotherapy neutropenia

First‑line supportive use in AML induction/consolidation

Chemotherapy Regimens and When CSF Support Is Recommended

Regimen	Context / example
Dose-dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)
Dose-dense AC (doxorubicin, cyclophosphamide) followed by dose-dense paclitaxel
Other chemotherapy regimens associated with ≥20% incidence of febrile neutropenia (FN)

Regimen/Approach	Coverage rationale / limitation
Dose-dense adjuvant chemotherapy for high‑risk breast cancer
High‑dose intensity MVAC for urothelial (bladder) cancer when efficacy data support use
Dose-dense regimens generally — permitted only when supported by convincing efficacy data or within appropriate clinical trial

Chemotherapy regimen	Guideline context / patient considerations
Dose‑dense AC → paclitaxel (adjuvant breast cancer)
CHOP‑R (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) — consider prophylaxis for patients aged ≥65 or with comorbidities
Regimens with overall FN risk ≥20% (primary prophylaxis recommended); regimens with 10–20% FN risk — consider prophylaxis if patient has additional risk factors

Policy Summary

PayerUnitedHealthcare

PolicyWhite Blood Cell Colony Stimulating Factors (for Indiana Only)

Policy CodePolicy N/A

Change TypeAdded product (Ryzneuta) and HCPCS code update (J9361)

Effective DateOct 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document febrile neutropenia risk assessment per InterQual and policy criteria when requesting CSF coverage.

SourceLink

On This Page

CSFs may be considered as adjunctive treatment for patients with fever and neutropenia who are at high risk for infection‑associated complications or have prognostic factors predictive of poor clinical outcomes; CSFs are not routine adjuncts to antibiotics for all FN patients.

Post-autologous stem-cell transplantation: Administration of CSFs after autologous stem‑cell transplantation to reduce duration of severe neutropenia is supported and recommended.post-autologous SCT

ASCO/NCCN

Allogeneic transplantation and mobilization: Use of single‑agent filgrastim or biosimilars is supported for allogeneic hematopoietic cell mobilization and granulocyte transfusion; CSFs may be used after allogeneic SCT to reduce duration of severe neutropenia.mobilization or post‑allogeneic SCT

NCCN/ASCO

PBPC mobilization: Filgrastim administered for mobilization (typical durations 5–7 days; reported doses 5–24 mcg/kg/day) is supported to mobilize peripheral blood progenitor cells for leukapheresis; sargramostim at 250 mcg/m2/day showed marked mobilization effects in cohort data.mobilization dosing per trials

Clinical trial and retrospective evidence

AML induction/consolidation support: G‑CSF (filgrastim) and GM‑CSF (sargramostim) shorten duration of severe neutropenia and infection‑related endpoints in AML induction/consolidation trials; evidence supports use to reduce duration of neutropenia and associated antibiotic use and hospitalization.post‑chemotherapy neutropenia

Randomized controlled trials

Acute radiation syndrome (hematopoietic): Use of filgrastim, pegfilgrastim, or sargramostim for hematopoietic syndrome of acute radiation syndrome is supported by animal efficacy data demonstrating improved survival and is recommended when clinical criteria are met.radiation exposure requiring CSF

Animal model efficacy and guideline consensus

life‑threatening infectious complications or poor antibiotic response

EORTC recommendation grade B

Post‑transplant use: CSFs should be administered after autologous stem‑cell transplantation to reduce duration of severe neutropenia and may be used after allogeneic transplantation to reduce duration of severe neutropenia; CSFs can be used to mobilize peripheral blood progenitor cells alone or with plerixafor depending on cancer and transplant type.post‑autologous or allogeneic transplant

ASCO evidence‑based recommendations

Hematopoietic syndrome of acute radiation syndrome: Ryzneuta and other indicated CSFs are considered proven and medically necessary to increase survival in patients acutely exposed to myelosuppressive doses of radiation when policy criteria are met.acute radiation exposure with hematopoietic syndrome

FDA indication cited and policy updated to include Ryzneuta

Consider alternativesConsider alternative, equally effective regimens not requiring CSF support when available

Overall FN risk threshold for prophylactic G-CSF

Overall prophylaxis threshold>= 20% overall FN risk is the threshold to recommend prophylactic G‑CSF

10–20% regimensFor regimens with 10–20% FN risk, assess patient risk factors to determine need for prophylaxis

Special considerationPrimary prophylaxis is also recommended when dose‑dense/intense chemotherapy with survival benefit is given

Listing of codes (see Applicable Codes) is for reference only and does not imply coverage or guarantee claim payment.
Verify member-specific benefits and applicable federal/state/contractual rules before billing.

Denial Risk

Guideline-Based Use Required

Use of CSFs inconsistent with guideline-based risk assessment may be noncovered. Requests for primary prophylaxis when the patient's FN risk is below guideline thresholds or that do not follow documented clinical risk assessment may be denied.

Primary prophylaxis generally recommended for ~20% or higher FN risk per ASCO/NCCN; use outside guideline-based risk thresholds requires strong justification.
Consider alternative equally effective chemotherapy regimens that do not require CSF support when available.

Denial Risk

Denial Triggers

Denial Triggers: Requests may be denied if they do not meet medical necessity criteria, lack required documentation, or do not use appropriate coding.

Requests lacking documentation of FN risk assessment prior to first chemotherapy cycle.
Requests without prescriber specialty or consultation when indicated (e.g., hematologist/oncologist for certain indications).
Incorrect or missing HCPCS/Q codes including newly added codes may delay or result in denial.

Billing Rule

Dosing and Coding Requirements

Prescriptions and dosing must follow the FDA-approved labeling; applicable HCPCS/Q codes and dosing units should be submitted with claims and authorization requests.

Dose and schedule must align with the FDA label for the specific CSF product.
Submit the appropriate HCPCS or Q-code (see Applicable Codes) with the claim/authorization.

Documentation Required

Risk Assessment Documentation Required

Risk Assessment Documentation: Document FN risk prior to the first cycle of chemotherapy, including disease, chemotherapy regimen, patient-specific risk factors, and treatment intent.

Document disease type and specific chemotherapy regimen (dose-dense/high-dose vs standard).
Document patient risk factors (age, organ dysfunction, prior therapies, marrow involvement, persistent neutropenia, comorbidities).
Document the estimated FN risk category (high, intermediate, low) and rationale for CSF use.

Documentation Required

Documentation and Benefit Governance

Documentation Requirements and Benefit Governing Rules: Coverage determinations are governed by federal, state, and contractual benefit requirements. Documentation supporting medical necessity must be retained and provided upon request.

Reference applicable federal/state/contractual requirements and the Indiana Medicaid SUPDL for product-preference rules when relevant.
Provide clinical notes, consultation reports, regimen details, dosing, and prior authorization submission documentation to support medical necessity.

Severe neutropenia confers high risk of infection-related complications and informs prophylaxis/treatment decisions

Primary prophylaxis definition

DefinitionAdministration of a colony‑stimulating factor (CSF) starting with the first chemotherapy cycle and continuing through subsequent cycles to prevent febrile neutropenia in patients at high risk (≈20% or greater)

IntentUsed to maintain chemotherapy dose intensity or density when FN risk would otherwise require dose reductions or delays

Assessment requiredDecision based on regimen FN risk and patient risk factors (age, organ dysfunction, marrow involvement, prior therapy, recent surgery, treatment intent)

Secondary prophylaxis definition

DefinitionAdministration of a CSF in subsequent chemotherapy cycles for patients who experienced a neutropenic complication in a prior cycle when dose reduction or delay would compromise outcomes

Typical indicationUsed when prior cycle caused FN or severe neutropenia and primary prophylaxis was not given

PurposeEnables continuation of full‑dose therapy to preserve disease‑free or overall survival when clinically necessary

FN abbreviation reference

AbbreviationFN = Febrile Neutropenia

UsageUsed throughout policy to refer to fever occurring with neutropenia as defined by temperature and ANC criteria

ContextGuideline recommendations for prevention and treatment are framed around FN risk categories

Biosimilar definition

DefinitionBiosimilar: a biologic highly similar to an FDA‑approved reference product with no clinically meaningful differences in safety or effectiveness

Regulatory standardMinor differences in clinically inactive components are allowable; biosimilars must demonstrate high similarity to the reference product

ExamplesFilgrastim and pegfilgrastim biosimilars (e.g., Nivestym, Nypozi, Fulphila, Fylnetra, Nyvepria) are referenced in the policy

first-line — 1 top-level node

Use with curative/adjuvant intent or dose‑dense regimens: When reductions in chemotherapy dose intensity or density are associated with poor prognosis or when treatment intent is curative, primary prophylactic G‑CSF is recommended to support regimen delivery and maintain dose intensity.regimens with survival benefit requiring dose‑dense delivery

First‑line supportive use to enable effective adjuvant/curative regimens