ModifiedBlue Cross Blue Shield - MassachusettsPolicy 105

Colony Stimulating Factors prior authorization and coverage

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This policy governs prior authorization, coverage criteria, and formulary status for colony stimulating factors (G-CSF and GM-CSF) for BCBSMA commercial and Medicare Advantage members when billed to the medical benefit; it informs providers about required documentation and delegated Medical Utilization Management to Carelon MBM.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyColony Stimulating Factors prior authorization and coverage

Policy CodePolicy 105

Change TypeFormulary updates and additions

Effective Date

Next Review Date

Key ActionSubmit prior authorization requests for colony stimulating factors via the Carelon MBM provider portal (or use MA Standard PA form #434 or call BCBSMA Pharmacy Operations for retail pharmacy) and document trials of formulary alternatives including names, strengths, dates, and reasons for failure.

SourceLink

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ModifiedBlue Cross Blue Shield - MassachusettsPolicy 105

Colony Stimulating Factors prior authorization and coverage

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Sign up for Blue Cross Blue Shield - Massachusetts Policy 105 alerts

Get alerted when Policy 105 changes without checking for updates manually.

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Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyColony Stimulating Factors prior authorization and coverage

Policy CodePolicy 105

Change TypeFormulary updates and additions

Effective Date

Next Review Date

SourceLink

POLICY UPDATE CHANGES

Added Ryzneuta to the policy.

Added Udenyca Onbody listing.

Moved Fulphila and Udenyca to preferred and moved Ziextenzo and Neulasta to Non-Formulary_Non-Covered.

Updated multiple CSF agents to Non-Formulary_Non-Covered (including Nivestym, Releuko, Fulphila, Fylnetra, Nyvepria, Rolvedon, Stimufend, & Udenyca).

DelegatedMedical Utilization Management delegated to Carelon MBM

PA requiredPrior authorization is required for listed growth factors

Two-stepNon-preferred agents require prior use of TWO preferred agents

Quality Care DosingQuantity limits applied per policy #621B

multipleCSF agents with formulary status changes in history

434MA standard medication PA form number

Coverage Criteria for Colony Stimulating Factors

Primary prophylaxis of febrile neutropenia

Covered when ALL of the following are met:

Primary prophylaxis prerequisites: The individual has a non-myeloid malignancy and is NOT receiving chemotherapy with radiation concurrently; AND Chemotherapy intent includes ONE of: curative intent (e.g., adjuvant treatment for early-stage disease), OR intent to prolong survival where a different regimen or dose reduction would reduce likelihood of reaching the treatment goal, OR intent is symptom management where a different regimen or dose reduction would reduce likelihood of reaching the treatment goal; AND the individual falls into ONE of the febrile neutropenia risk categories described below.

Risk category (one required): High risk of febrile neutropenia (>=20% based on chemotherapy regimen per Carelon MBM Febrile Neutropenia Risk Guideline) OR Intermediate risk (10–20% based on regimen) PLUS at least ONE significant risk factor: age >65; poor performance status (ECOG 3–4 but chemotherapy still indicated); preexisting neutropenia (for example from marrow damage or tumor infiltration; ANC <1500/mm3); prior febrile neutropenia episode; liver dysfunction (bilirubin >=1.0 or elevated LFTs); presence of open wounds or active infections when chemotherapy cannot be delayed; renal dysfunction (CrCl <50 mL/min); poor nutritional status (albumin <3.5 g/dL or BMI <20); active HIV requiring therapy; high tumor volume/high symptom burden; or multiple serious comorbid conditions.

Secondary prophylaxis of febrile neutropenia

Covered when ALL of the following are met:

Secondary prophylaxis: Previous neutropenic complication occurred in the absence of primary prophylaxis; AND a change to the regimen (including dose reduction, schedule change, or change in therapy) would be expected to compromise patient outcome, particularly in the setting of curative intent.

Adjunctive treatment of febrile neutropenia

Medically necessary when ANY of the following risk factors are present (and no growth factor used within the same cycle):

Adjunctive treatment factors: Age >65; expected neutrophil recovery delayed (>10 days); profound neutropenia (<0.1 x 10^9/L); active pneumonia; invasive fungal or other opportunistic infection; sepsis syndrome (hypotension and/or multi-organ damage/dysfunction); onset of fever during inpatient stay.

Covered indications by growth factor type

Specific indications covered for each product when requirements are met:

Granix and Zarxio indications: Acute lymphocytic leukemia (ALL) — use after start of induction or first post‑remission chemotherapy course; Acute myeloid leukemia (AML) — use after induction, reinduction, or consolidation; Aplastic anemia (moderate or severe); Hairy cell leukemia to treat severe neutropenia; Hematopoietic stem cell transplant to treat delayed or failed engraftment, to promote myeloid recovery, or to mobilize stem cells for collection; Myelodysplastic syndrome (MDS) to treat neutrophil count <500/mm3 or recurrent infection; Radiation exposure after accidental/intentional irradiation >2 Gy or following radiation therapy if prolonged delays expected; Support for dose-dense or dose-intensive chemotherapy in specified scenarios (adjuvant high‑risk breast cancer with anthracycline/cyclophosphamide followed by paclitaxel; high‑dose M‑VAC in urothelial cancer; chemotherapy intensification for localized Ewing sarcoma).

Fulphila and Udenyca indications: Acute lymphocytic leukemia (ALL) — use after start of induction or first post‑remission course; Hematopoietic stem cell transplant to treat delayed or failed engraftment or to promote myeloid recovery; Myelodysplastic syndrome (MDS) to treat neutrophil count <500/mm3 or recurrent infection; Radiation exposure indications as above; Support for dose‑dense chemotherapy in scenarios including high‑risk breast cancer adjuvant anthracycline/cyclophosphamide followed by paclitaxel, high‑dose M‑VAC, and chemotherapy intensification for localized Ewing sarcoma.

The policy specifies that the use of multiple WBC growth factor agents for prophylaxis and/or adjunctive treatment within the same chemotherapy cycle is not clinically indicated. When multiple agents are used within a cycle, those uses are not covered by this policy. This aligns with the Covered Indications and exclusions for colony stimulating factors and is intended to prevent concurrent duplication of G‑CSF/GM‑CSF therapies during a single chemotherapy cycle.

Policy history documents multiple formulary status changes over time. Notable entries include that on 1/2025 Fulphila and Udenyca were moved to preferred while Ziextenzo and Neulasta were moved to Non‑Formulary_Non‑Covered. Earlier and subsequent actions list additions of products (for example, Udenyca Onbody added in 8/2025 and Ryzneuta added 9/30/2025) and other revisions that changed the non‑formulary or non‑covered status of multiple agents.

Chemotherapy Regimens and Indications Covered

Regimen / Scenario	Example Indications where CSF Support is Covered	Coverage Note
Adjuvant high‑risk breast cancer: anthracycline (doxorubicin or epirubicin) + cyclophosphamide followed by paclitaxel	Support for dose‑dense or dose‑intense chemotherapy in the adjuvant high‑risk breast cancer setting	Covered when policy primary prophylaxis or secondary prophylaxis criteria are met (see coverage criteria).
High‑dose intensity MVAC (HD‑M‑VAC) for urothelial cancer	Support for dose‑intense regimens such as HD‑M‑VAC	Covered as CSF support when requirements for prophylaxis/treatment are satisfied.
Chemotherapy intensification for newly diagnosed localized Ewing sarcoma (interval‑compressed/dose‑dense regimens)	Support for dose‑intense or interval‑compressed regimens in Ewing sarcoma	Covered to maintain planned dose intensity when CSF use is indicated per regimen risk and patient factors.

Agent (generic / brand)	Examples of Product References (product information / history)	Typical Use per Policy
Tbo‑filgrastim (Granix)	Granix [Product Information] (see References)	May be covered for indications listed (ALL, AML, HSCT, MDS, radiation exposure, and support for dose‑dense/dose‑intense chemotherapy when criteria met).
Filgrastim (Zarxio)	Zarxio [Product Information] (see References)	Covered for indications listed including hematologic malignancies, HSCT support, MDS, radiation exposure, and dose‑dense chemotherapy support when requirements are met.
Pegfilgrastim biosimilars (Fulphila; Udenyca / Udenyca Onbody)	Fulphila [Product Information]; Udenyca Onbody listed in Policy History; additional product listings in References and Policy History	May be covered for ALL, HSCT support, MDS, radiation exposure, and support for dose‑dense chemotherapy when policy criteria are satisfied.
Sargramostim (Leukine)	Leukine [Product Information] (see References)	Covered for specified indications including ALL, AML (in older adults per labeling), HSCT support, MDS, radiation exposure, and dose‑dense chemotherapy support when requirements are met.
Other pegfilgrastim and filgrastim biosimilars (e.g., Rolvedon, Fylnetra, Stimufend, Ryzneuta)	Product information entries for Rolvedon, Fylnetra, Stimufend, and Ryzneuta listed in References/Policy History	Coverage and formulary status vary by specific agent and policy history; refer to policy history and formulary status for current preferred or non‑covered designations.

Line of Therapy Guidance

first-line

first-line: Use after start of induction or first post‑remission chemotherapy course for indications such as ALL and certain transplant‑related settings (see growth factor–specific indications).

Provider Actions — Prior Authorization and Documentation

Prior Authorization

Prior authorization required — submit via Carelon MBM or BCBSMA Pharmacy Operations

Prior authorization is required for colony stimulating factors billed to the medical benefit; requests for medical-benefit administration must be submitted via the Carelon MBM provider portal (through Blue Cross Provider Central eTools or directly to Carelon's ProviderPortal) or by calling Carelon when applicable. Retail/specialty outpatient pharmacy requests should be submitted to BCBSMA Clinical Pharmacy Operations using the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm or print/fax Form #434) or by calling BCBSMA Pharmacy Operations at 1-800-366-7778.

Carelon MBM portal: access via Blue Cross Blue Shield MA Provider Central eTools > Carelon Medical Benefits Management or directly at Carelon's ProviderPortal (registration required).
Carelon phone (when applicable): 1-866-745-1783 for Carelon portal assistance.
Retail/specialty pharmacy PA: submit Massachusetts Standard Form for Medication Prior Authorization Requests (eForm) or print/fax Form #434; or call BCBSMA Pharmacy Operations at 1-800-366-7778.

Step Therapy

Clinical Thresholds and Coding References

ANC thresholds / lab values

ANC threshold for neutropeniaAbsolute neutrophil count (ANC) < 500 cells/mm3

ANC indicating risk / monitoringANC ≤ 1000 cells/µL (and expected to fall below 500 cells/µL within 48 hours)

Profound neutropeniaProfound neutropenia defined as ANC < 0.1 x10^9 (i.e., <100 cells/µL)

Additional laboratory/clinical thresholds referenced for risk stratificationBilirubin ≥ 1.0 mg/dL; creatinine clearance < 50 mL/min; albumin < 3.5 g/dL; age > 65 years

Definitions

Febrile neutropenia

Febrile neutropenia definitionOral temperature > 38.3°C (101.0°F) plus neutropenia (ANC ≤ 1000 cells/µL or ANC < 1000 and expected to fall below 500 cells/µL within 48 hours)

Clinical context for adjunctive treatmentAdjunctive G-CSF may be medically necessary when risk factors such as age >65, delayed neutrophil recovery (>10 days), profound neutropenia (<0.1 x10^9), active pneumonia, invasive fungal/opportunistic infection, sepsis syndrome, or onset of fever during inpatient stay are present

Example ANC thresholds cited for preexisting neutropeniaPreexisting neutropenia example given as ANC < 1500 cells/mm3 for risk stratification

Granulocyte‑colony stimulating factor (G‑CSF)

Definition of G-CSF agentsMedications (filgrastim, pegfilgrastim and biosimilars) that stimulate neutrophil production to prevent or treat chemotherapy-induced neutropenia and febrile neutropenia

Background

Colony stimulating factors (G‑CSF and GM‑CSF) are used to prevent or treat chemotherapy‑induced neutropenia and febrile neutropenia and to support myeloid recovery in hematologic conditions and transplant settings. The policy aligns authorization and coverage with Carelon MBM clinical guidance and lists specific covered indications — for example, use after induction or first post‑remission chemotherapy in acute lymphocytic leukemia (ALL), use in selected acute myeloid leukemia (AML) settings, hematopoietic stem cell transplant indications (to treat delayed or failed engraftment, to promote recovery, or to mobilize stem cells), myelodysplastic syndrome (MDS) when ANC is low or infections are recurrent, radiation exposure above 2 Gy, and support for dose‑dense or dose‑intense chemotherapy regimens (including adjuvant high‑risk breast cancer anthracycline/cyclophosphamide followed by paclitaxel, HD‑M‑VAC in urothelial cancer, and chemotherapy intensification for localized Ewing sarcoma). The background also reflects that multiple products and biosimilars are tracked in the policy and that formulary statuses have changed over time per the policy history.

Policy Revision History

2025-09-30additionLatest

Added Ryzneuta to the policy.

2025-08addition

Added Udenyca Onbody listing.

2025-01formulary_change

Moved Fulphila and Udenyca to preferred and moved Ziextenzo and Neulasta to Non-Formulary_Non-Covered.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyColony Stimulating Factors prior authorization and coverage

Policy CodePolicy 105

Change TypeFormulary updates and additions

Effective Date

Next Review Date

SourceLink

On This Page

Leukine indications:

Acute lymphocytic leukemia (ALL) — use after start of induction or first post‑remission course; Acute myeloid leukemia (AML) — use after induction/reinduction for individuals >55 years; Hematopoietic stem cell transplant to treat delayed or failed engraftment, to promote myeloid recovery, or to mobilize stem cells; Myelodysplastic syndrome (MDS) to treat neutrophil count <500/mm3 or recurrent infection; Radiation exposure indications as above; Support for dose‑dense chemotherapy in scenarios including high‑risk breast cancer adjuvant anthracycline/cyclophosphamide followed by paclitaxel, high‑dose M‑VAC, and chemotherapy intensification for localized Ewing sarcoma. Note: The use of multiple WBC growth factor agents for prophylaxis and/or adjunctive treatment within a given chemotherapy cycle is not clinically indicated; medications above are not covered for conditions not listed.

Step requirement for non-preferred agents — two preferred agents required

Non-preferred (NFNC) colony stimulating factor products require prior use of TWO preferred agents before a non-preferred product will be considered, and the request must otherwise meet applicable prior authorization criteria.

Examples in the policy list multiple NFNC products that state: “Requires prior use of TWO Preferred medication AND must meet PA criteria below.”

Prior Authorization

Prior authorization submission methods — eForm #434, fax, phone, or Carelon portal

Outpatient retail or specialty pharmacy prior authorization requests must be submitted to BCBSMA Clinical Pharmacy Operations using the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm or print/fax Form #434) or by calling BCBSMA Pharmacy Operations at 1-800-366-7778; medical-benefit administration requests must be submitted via Carelon MBM provider portal (or by phone when applicable).

Retail/specialty pharmacy: Massachusetts Standard Form for Medication Prior Authorization Requests (eForm) or Form #434 (print/fax).
BCBSMA Pharmacy Operations phone: 1-800-366-7778 for verbal PA/formulary exception requests.
Medical-benefit administration: submit via Carelon MBM through Blue Cross Provider Central eTools or Carelon’s ProviderPortal; Carelon support phone 1-866-745-1783 when applicable.

Step Therapy

Step therapy / formulary exception — two formulary alternatives required before non-covered agent

For medications that are non-covered or non-formulary, the member must have prior treatment failure with, or a contraindication to, at least two covered formulary alternatives when available before coverage of the non-covered agent is considered.

Policy explicitly requires prior failure with or contraindication to at least two covered formulary alternatives for non-covered medications.
Consideration should be given to equally effective alternatives that do not require CSF support when available.

Step Therapy

Formulary alternative trial requirement — show trials or request individual consideration

Requests must demonstrate trial and failure of formulary alternative(s) unless an exception (individual consideration) is granted based on documented clinical reasons; prescription claims may be used to establish prior use of formulary alternatives.

If prescription claims data do not establish prior use, the provider must supply additional documentation.
Individual consideration requests should include supporting clinical documentation and rationale for exception.

Documentation Required

Provider documentation requirements — list name, strength, dates, and failure details

Provider documentation must include the name and strength of formulary alternatives tried and failed (including dates if available) and specifics regarding the treatment failure or the clinical reason preventing switch to a formulary alternative.

If alternatives were tried, include dates of therapy and reason for failure.
Provide specifics around the clinical reason preventing trial/switch to a formulary alternative (e.g., contraindication, adverse reaction).

Documentation Required

Required provider documentation for PA and exceptions — include trial details and supporting clinical evidence

For prior authorization and exception requests, document the name and strength of formulary alternatives tried and failed (including dates if available), specifics of treatment failure, and provide clinical rationale; include additional supporting materials (clinical notes, literature, guideline references, compendia) for individual consideration.

Include clinical notes or statements and relevant literature or guideline references when requesting an exception.
BCBSMA may use prescription claims to verify prior use; if claims are insufficient, provide documentation showing fills or clinical evidence of use.

Denial Risk

Documentation of prior trials required — lacking trial evidence may lead to denial

Failure to document prior trials of formulary alternatives (names, strengths, dates, and reasons for failure) or inability to show prescription evidence of preferred formulary medication use may result in denial of the request.

Policy states that inability to show prescription claims demonstrating use of preferred formulary medications may lead to denial and additional information may be requested.

Denial Risk

Insufficient documentation of formulary alternative trial — may trigger denial/non-coverage

Insufficient documentation of trials and failures of formulary alternatives — including name, strength, dates (if available), and specifics of treatment failure — may result in non-coverage or denial unless adequate evidence or an approved exception is provided.

Providers should ensure all trial details and reasons for failure are clearly documented; BCBSMA may request further information if prescription claims do not establish prior use.

Examples of G-CSF products referenced in policy

Filgrastim (e.g., Neupogen, Zarxio), pegfilgrastim products (e.g., Neulasta, Fulphila, Udenyca), and other branded/biosimilar agents listed in product references

Indications captured in policy for G-CSF useProphylaxis and treatment of chemotherapy-induced neutropenia/febrile neutropenia, support for dose-dense/dose-intense regimens, stem cell mobilization, and select hematologic indications

2024-07formulary_change

Updated multiple CSF agents (Nivestym, Releuko, Fulphila, Fylnetra, Nyvepria, Rolvedon, Stimufend, and Udenyca) to Non-Formulary_Non-Covered.