Colorado Rocky Mountain Health Plans CSF Coverage Update

Coverage Criteria and Medical Necessity

Preferred product exception — Long-acting pegfilgrastim

Covered when ONE of the following is met (for non-preferred pegfilgrastim products):

Pegfilgrastim non-preferred exception: Either: (1) Both: history of a trial of adequate dose and duration of Neulasta or Udenyca resulting in minimal clinical response; and physician attests that clinical response would be expected to be superior with the requested pegfilgrastim biosimilar; OR (2) Both: history of intolerance, contraindication, or adverse event to Neulasta or Udenyca; and physician attests that the same intolerance, contraindication, or adverse event would not be expected to occur with the requested pegfilgrastim biosimilar.

Used to permit Fulphila, Fylnetra, Nyvepria, Rolvedon, Ryzneuta, Stimufend, Ziextenzo or other pegfilgrastim biosimilars.

Preferred product exception — Short-acting filgrastim

Covered when ONE of the following is met (for non-preferred filgrastim products):

Filgrastim non-preferred exception: Either: (1) Both: history of a trial of adequate dose and duration of Zarxio or Nivestym resulting in minimal clinical response; and physician attests that clinical response would be expected to be superior with the requested filgrastim biosimilar; OR (2) Both: history of intolerance, contraindication, or adverse event to Zarxio or Nivestym; and physician attests that the same intolerance, contraindication, or adverse event would not be expected to occur with the requested filgrastim biosimilar.

Used to permit Granix, Neupogen, Nypozi, Releuko or other filgrastim biosimilars.

Bone marrow/stem cell transplant

Covered when ONE of the following is met:

BMT/PSCT indications: Patient has non‑myeloid malignancy and is undergoing myeloablative chemotherapy followed by autologous or allogeneic bone marrow transplant; OR used for mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; OR patient has had a peripheral stem cell transplant and received myeloablative chemotherapy.

Applies to Leukine, Neupogen, Nivestym, Nypozi, Releuko, Zarxio.

Acute Myeloid Leukemia (AML) — induction or consolidation

Covered when ALL of the following are met:

AML criteria: (1) Diagnosis of acute myeloid leukemia (AML); AND (2) One of: patient achieved complete remission after induction therapy; or patient is receiving consolidation chemotherapy; or patient is receiving specified relapsed/refractory regimens (for example fludarabine + cytarabine ± idarubicin, or cladribine + cytarabine ± mitoxantrone or idarubicin).

Applies to Leukine, Neupogen, Nivestym, Nypozi, Releuko, Zarxio; randomized trial evidence supports reduced duration of severe neutropenia and faster ANC recovery.

Primary prophylaxis of chemotherapy‑induced febrile neutropenia

Covered when ONE of the following is met:

Primary prophylaxis criteria: Patient is receiving dose‑dense MVAC for bladder cancer; OR dose‑dense AC followed by dose‑dense paclitaxel for breast cancer; OR patient is receiving a chemotherapy regimen associated with > 20% incidence of febrile neutropenia (FN).> 20% FN incidence

Applies to listed pegfilgrastim and filgrastim products; aligns with NCCN/ASCO recommendations to provide primary prophylaxis when overall FN risk ≥20%.

Primary prophylaxis — intermediate FN risk (10–20%)

Covered when ALL of the following are met:

Intermediate risk with risk factors: (1) Patient is receiving chemotherapy regimens associated with a 10–20% incidence of febrile neutropenia; AND (2) Patient has one or more additional risk factors such as persistent neutropenia from prior therapy (ANC < 500/mcL or < 1,000/mcL with predicted decline to ≤ 500/mcL in 48 hours), liver dysfunction (bilirubin > 2.0 mg/dL), renal dysfunction (creatinine clearance < 50 mL/min), or age > 65 years receiving full chemotherapy dose intensity.10–20% FN incidence

Individualized assessment per NCCN/EORTC guidance; consider prophylaxis when regimen risk plus patient factors increase overall FN risk.

Secondary prophylaxis of febrile neutropenia

Covered when ONE of the following is met AND additional conditions as listed:

Secondary prophylaxis qualifying scenarios: Patient is receiving myelosuppressive anticancer drugs given with curative intent (adjuvant/neoadjuvant/curative chemotherapy); OR receiving myelosuppressive anticancer drugs for definitive therapy (eg bridge to stem cell transplant or definitive surgery for oligometastatic disease); OR patient is receiving myelosuppressive anticancer drugs where primary prophylaxis is indicated.

AND patient must meet supporting history criteria such as prior documented neutropenic event (eg prior FN or dose‑limiting neutropenia causing delay) or meet FDA‑label guidance; secondary prophylaxis recommended when prior neutropenic complication occurred and continuation of full‑dose therapy is needed.

Treatment of febrile neutropenia (off‑label)

Covered when ALL of the following are met:

Treatment of FN criteria: (1) Diagnosis of febrile neutropenia; AND (2) Patient has not received long‑acting prophylactic pegfilgrastim in the last 14 days; AND (3) Patient has one or more high‑risk features for infection‑associated complications such as sepsis syndrome, age > 65 years, ANC < 100/mcL, neutropenia expected to be > 10 days in duration, pneumonia, invasive fungal infection, or hospitalization at the time of fever; AND (4) Additional infectious risk factors or prior episodes of FN may be present.ANC < 100/mcL as high risk

Treatment use is considered off‑label and reserved for high‑risk patients per ASCO/EORTC guidance; applies to listed pegfilgrastim and filgrastim products.

Severe Chronic Neutropenia (SCN)

Covered when ALL of the following are met:

SCN criteria: (1) Diagnosis of severe chronic neutropenia (congenital, cyclic, or idiopathic) with chronic ANC ≤ 500 neutrophils/mcL; AND (2) Medication is dosed in accordance with United States FDA‑approved labeling; AND (3) Prescribed by or in consultation with a hematologist or oncologist.ANC ≤ 500/mcL

Applies to Neupogen, Nivestym, Nypozi, Releuko, Zarxio.

Hematopoietic syndrome of acute radiation syndrome (ARS)

Covered when ALL of the following are met:

ARS hematopoietic syndrome criteria: (1) Patient has been acutely exposed to myelosuppressive doses of radiation; AND (2) Medication is dosed in accordance with United States FDA‑approved labeling; AND (3) Prescribed by or in consultation with a hematologist or oncologist.

Applies to Fulphila, Fylnetra, Leukine, Neulasta, Neupogen, Nivestym, Nypozi, Nyvepria, Releuko, Rolvedon, Ryzneuta, Stimufend, Udenyca, Zarxio, and Ziextenzo.

Guideline-concordant coverage criteria

Covered when criteria mirror guideline recommendations (examples summarized):

Primary prophylaxis: Patient is scheduled to receive myelosuppressive chemotherapy with overall FN risk >20% OR is receiving dose‑dense chemotherapy where CSF support is appropriate to maintain dose intensity and proven survival benefit.FN risk >20%

Based on NCCN, ASCO, and EORTC guidance.

Secondary prophylaxis: Patient experienced a neutropenic complication (eg febrile neutropenia or dose‑limiting neutropenia) from a prior cycle and dose reduction or delay would compromise disease‑free or overall survival.history of neutropenic complication

ASCO recommends secondary prophylaxis in these scenarios.

Treatment of FN: Consider CSF for patients with fever and neutropenia who are at high risk for infection‑associated complications or have prognostic factors predictive of poor outcomes; do not routinely use CSF in afebrile neutropenia.

Evidence-supported indications

Indications supported by clinical trial evidence (examples):

AML induction/consolidation: Use of filgrastim or sargramostim to reduce time to neutrophil recovery and duration of fever following induction or consolidation chemotherapy in AML; randomized trials demonstrated shortened duration of severe neutropenia and faster ANC recovery.ANC recovery endpoints

Randomized trial evidence summarized in labeling and trials.

Bone marrow transplantation: Use of filgrastim or sargramostim after autologous or allogeneic bone marrow transplantation reduces duration of severe neutropenia, shortens hospitalization, and decreases febrile neutropenia in randomized studies.post‑BMT neutropenia

Multiple randomized controlled trials cited showing reductions in days of severe neutropenia and FN.

Prophylactic and therapeutic use of CSFs

Covered when guided by guideline‑recommended risk and clinical scenarios

Primary prophylaxis for FN: G‑CSF prophylaxis is appropriate when the overall risk of febrile neutropenia from a chemotherapy regimen is ≥20% OR when a dose‑dense/intense chemotherapy regimen with demonstrated survival benefit is being given and maintaining dose intensity is important.FN risk >=20%; dose‑dense regimens with survival benefit

EORTC and ASCO recommendations.

Consider prophylaxis at 10–20% regimen risk: When regimen FN risk is 10–20%, consider G‑CSF if patient has additional risk factors (eg age ≥65, comorbidities, prior FN, persistent neutropenia).FN risk 10–20% with clinical risk factors

EORTC recommends individualized assessment.

Therapeutic use in ongoing FN: G‑CSF treatment for patients with ongoing febrile neutropenia is reserved for special situations such as lack of response to appropriate antibiotics and development of life‑threatening infectious complications.

Ryzneuta — Covered Indications

Ryzneuta coverage — medical necessity when criteria are met

Indications: Ryzneuta (efbemalenograstim alfa‑vuxw) is medically necessary when policy criteria are met for: hematopoietic syndrome of acute radiation syndrome; primary prophylaxis of chemotherapy‑induced febrile neutropenia; secondary prophylaxis of febrile neutropenia; and treatment of febrile neutropenia.

Added to list of covered CSF products per policy revision.

Exceptions for Continuing Ryzneuta

Conditions allowing continued use of Ryzneuta despite preferred product policy

Exceptions to preferred product requirement: Members already on Ryzneuta may continue only if they meet one of two alternative exception pathways: (1) prior adequate trial of Neulasta or Udenyca resulted in minimal clinical response AND physician attests Ryzneuta is expected to be superior; OR (2) history of intolerance, contraindication, or adverse event to Neulasta or Udenyca AND physician attests the same would not be expected with Ryzneuta.

Physician attestation required; otherwise member must change to preferred pegfilgrastim products.

Any U.S. Food and Drug Administration‑approved white blood cell colony stimulating factor (CSF) product that is not named in this policy will be considered non‑preferred until it is reviewed by UnitedHealthcare. This includes any pegfilgrastim, filgrastim, tbo‑filgrastim, sargramostim, or other leukocyte growth factor product not listed by name in the Coverage Rationale section. Requests for coverage of such products should follow the prior authorization and preferred‑product exception processes described in the policy.

The American Society of Clinical Oncology (ASCO) guidance states that CSFs should not be routinely used for patients with neutropenia who are afebrile. ASCO also recommends that CSFs should not be routinely used as adjunctive therapy with antibiotics for febrile neutropenia, except in patients who are at high risk for infection‑associated complications or who have prognostic factors predictive of poor clinical outcomes; in those high‑risk situations CSFs may be considered.

For pediatric patients, ASCO guidance indicates that the use of CSFs is generally protocol‑driven and should be limited to scenarios such as primary prophylaxis when the risk of febrile neutropenia is high or to enable delivery of dose‑intense regimens with proven survival benefit. ASCO specifically advises that 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 an infection.

Ryzneuta (efbemalenograstim alfa‑vuxw) is included among listed CSF products but is subject to the policy's preferred‑product requirements. Members currently receiving Ryzneuta who do not meet the Preferred Product Criteria are required to transition to a preferred pegfilgrastim product (Neulasta or Udenyca) unless they meet one of the exception pathways described in the policy (for example, documented trial failure or intolerance with attestation).

Approval of any filgrastim or pegfilgrastim product under this policy is contingent on meeting the applicable Diagnosis‑Specific Criteria and any Preferred Product Criteria. If the requested product does not meet those criteria — for example, absence of an indication that satisfies the diagnosis‑specific coverage rules or failure to document required prior trials/attestations for non‑preferred products — the request may be considered not medically necessary and denied.

ASCO guidance does not support routine CSF use for afebrile neutropenia and advises against routine adjunctive CSF use with antibiotics for febrile neutropenia except in patients at high risk for complications. These recommendations underpin this policy's stance that prophylactic or therapeutic CSF use be limited to guideline‑recommended scenarios and documented high‑risk situations rather than used routinely in low‑risk febrile neutropenia or afebrile neutropenia.

ASCO states that dose‑dense regimens with CSF support should be used only when supported by convincing efficacy data or within a clinical trial. While CSF support is appropriate for dose‑dense adjuvant breast cancer regimens and certain high‑dose intensity urothelial regimens, there are limited and conflicting data for routine use of CSFs with dose‑dense regimens in non‑Hodgkin lymphoma; therefore CSFs should not be used routinely for NHL dose‑dense regimens unless specific evidence supports benefit.

Applicable Codes and Definitions

Applicable HCPCS/CodesHCPCS

J1442	Injection, filgrastim, (G-CSF), excludes biosimilars, 1 microgram
J1447	Injection, tbo-filgrastim, 1 microgram
J1449	Injection, eflapegrastim-xnst, 0.1 mg
J2506	Injection, pegfilgrastim, 0.5 mg
J2820	Injection, sargramostim (GM-CSF), 50 mcg
J3490	Unclassified drugs
J3590	Unclassified biologics
J9361	Injection, efbemalenograstim alfa-vuxw, 0.5 mg
J9999	Not otherwise classified, antineoplastic drug
Q5101	Injection, filgrastim-sndz, biosimilar, (Zarxio), 1 microgram

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Applicable HCPCS CodesHCPCS

J9361

added HCPCS code (specific description not provided in excerpt)

Primary prophylaxis FN incidence threshold

Primary prophylaxis FN incidence threshold> 20% incidence of febrile neutropenia

Dose‑dense regimen examplesDose‑dense MVAC for bladder cancer; dose‑dense AC → dose‑dense paclitaxel for breast cancer

Applies to listed CSF productsApplies to pegfilgrastim and filgrastim products named in policy (e.g., Neulasta, Fulphila, Zarxio)

Febrile neutropenia definition thresholds

Fever thresholdSingle oral temperature ≥ 38.3 °C or ≥ 38.0 °C sustained over 1 hour

Neutropenia threshold (absolute)ANC < 500 neutrophils/mcL

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required and Applicable Code

Prior authorization is required for all pegfilgrastim and filgrastim products. Approvals for non-preferred products (including Ryzneuta and other listed biosimilars) are granted only when the Preferred Product Criteria and the Diagnosis‑Specific Criteria are met. Applicable billing code: HCPCS J9361 (Ryzneuta) has been added — include appropriate HCPCS on prior auth requests.

Prior authorization required for all CSF requests.
HCPCS: J9361 (Ryzneuta) — include on claim/prior auth submission.

Documentation Required

Prior Authorization: Clinical Risk Assessment Documentation

Prior authorization for colony‑stimulating factor (CSF) use must document an assessment of febrile neutropenia (FN) risk prior to the first chemotherapy cycle. Use established guidance (NCCN/ASCO/EORTC) to determine overall FN risk (high >20%, intermediate 10%–20%, low <10%) and document chemotherapy regimen risk, treatment intent, and patient factors.

Definitions and Clinical Thresholds

Febrile Neutropenia

Fever criterion (oral)Temperature ≥ 38.3 °C orally or 38.0 °C over 1 hour

Neutropenia absolute thresholdANC < 500 neutrophils/mcL

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

Neutropenia / Severe Neutropenia

Neutropenia (general)ANC < 1500 neutrophils/mcL

Severe neutropeniaANC < 500 neutrophils/mcL

ContextDefinitions used to stratify FN risk and guide CSF use

Chemotherapy Regimens and Indications for CSF Support

Regimen	Indication / Notes	Coverage
AML induction or consolidation regimens (examples)	Use with AML induction or consolidation; also for certain relapsed/refractory regimens such as fludarabine + cytarabine ± idarubicin, cladribine + cytarabine ± mitoxantrone or idarubicin.	Covered
Agents	Applies to Leukine, Neupogen, Nivestym, Nypozi, Releuko, Zarxio per AML criteria	Covered

Regimen	Indication / Notes	Coverage
Dose‑dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)	Used in bladder cancer where dose‑dense scheduling is employed; primary prophylaxis with CSF indicated per guideline-concordant recommendations.	Covered
Dose‑dense AC → dose‑dense paclitaxel (doxorubicin + cyclophosphamide then paclitaxel)	Adjuvant dose‑dense breast cancer regimens where maintaining dose intensity is important; primary prophylaxis indicated.	Covered

Regimen	Indication / Notes	Coverage
Dose‑dense or high‑dose intensity chemotherapy regimens	Support dose‑dense or high‑dose intensity regimens where CSF support is indicated (e.g., adjuvant high‑risk breast cancer dose‑dense regimens); use when evidence supports survival benefit or to maintain dose intensity.	Covered

Regimen	Indication / Notes	Coverage
Dose‑dense adjuvant chemotherapy for high‑risk breast cancer	Prophylactic G‑CSF to maintain dose intensity when dose‑dense adjuvant regimens have demonstrated survival benefit; follow guideline recommendations and assess patient risk factors.	Covered

Regimen	Indication / Notes	Coverage
High‑dose intensity MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)	High‑dose intensity MVAC in urothelial cancer where CSF support is used to reduce duration of severe neutropenia and support delivery of intensive chemotherapy.	Covered

Regimen	Indication / Notes	Coverage
Dose‑dense regimens in non‑Hodgkin lymphoma (NHL)	Limited and conflicting evidence for routine use of CSF support in dose‑dense NHL regimens; CSF support not routinely recommended absent convincing efficacy data.	Not routinely recommended

Product	Indications (when policy criteria met)	Coverage
Ryzneuta (efbemalenograstim alfa‑vuxw)	Primary prophylaxis of chemotherapy‑induced febrile neutropenia; secondary prophylaxis of febrile neutropenia; treatment of febrile neutropenia; hematopoietic syndrome of acute radiation syndrome — coverage contingent on meeting policy criteria and required physician attestation for preferred‑product exceptions.	Covered

Line of Therapy Designations

first-line | consolidation

first-line | consolidation: Use during induction (to support neutrophil recovery) and during consolidation chemotherapy for AML, and during specified relapsed/refractory AML regimens as described in policy.

first-line

first-line: Primary prophylaxis prior to the first cycle of myelosuppressive chemotherapy when regimen and patient factors indicate overall FN risk requiring prophylaxis (eg ≥20% or dose‑dense regimens with demonstrated benefit).

second-line

second-line: Secondary prophylaxis after a prior neutropenic complication (eg FN or dose‑limiting neutropenia) when dose reduction or delay would compromise outcomes, or per FDA label guidance for non‑curative intent settings as specified.

Background and Clinical Evidence

Neutropenia is defined as an abnormally low neutrophil count which increases susceptibility to infection. Febrile neutropenia (FN) describes the combination of fever and neutropenia and is a major complication of myelosuppressive chemotherapy. CSFs — including granulocyte colony‑stimulating factors (G‑CSFs) and granulocyte‑macrophage CSFs — reduce the duration and severity of neutropenia, decrease the incidence of FN in appropriate settings, and can enable delivery of intensive or dose‑dense chemotherapy regimens when clinically indicated.

Policy Revision History

2025-10-01policy_updateLatest

Added Ryzneuta (efbemalenograstim alfa-vuxw) to the list of applicable CSFs, added HCPCS code J9361, and specified that members currently on Ryzneuta must change therapy to Neulasta or Udenyca unless they meet Preferred Product Criteria exceptions (including required physician attestation and prior trial/intolerance pathways).

OpenPayer

White Blood Cell Colony Stimulating Factors

Coverage Criteria and Medical Necessity

Applicable Codes and Definitions

Prior Authorization, Documentation, and Step Therapy

Definitions and Clinical Thresholds

Chemotherapy Regimens and Indications for CSF Support

Line of Therapy Designations

Background and Clinical Evidence

Policy Revision History