CurrentNeighborhood Health Plan of Rhode IslandPolicy UM ONC_1072

Myeloid Growth Factors (MGFs)

Defines accepted indications, exclusions, dosing limits, and utilization management requirements for myeloid growth factors (short- and long-acting filgrastim products, pegfilgrastim products, sargramostim, eflapegrastim, efbemalenograstim) for cancer patients; applies to medication requests processed by Evolent for Neighborhood Health Plan of Rhode Island members.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyMyeloid Growth Factors (MGFs)

Policy CodePolicy UM ONC_1072

Change TypeNo material changes

Effective DateAugust 30, 2024

Next Review DateN/A

Key ActionSubmit prior authorization with regimen FN risk category and supporting clinical documentation per NCCN/ASCO or FDA labeling.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

28pages

NCCN/ASCOguidelines referenced

Less than 10%low risk threshold

Low/Int/HighFN risk categories

Coverage Criteria for Myeloid Growth Factors

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PBSC Mobilization

Covered when ANY of the following are met (PBSC mobilization):

PBSC mobilization: Short-acting MGF (e.g., filgrastim/filgrastim biosimilar/sargramostim) used for peripheral blood stem cell (PBSC) mobilization prior to and during leukapheresis in members undergoing an autologous PBSC collection and therapy.

Prophylaxis/Prevention of Febrile Neutropenia

Covered when ALL of the following are met (Prophylaxis/Prevention of Febrile Neutropenia):

Primary prophylaxis - high risk chemo: Member has a solid tumor or non-myeloid malignancy and MGF will be used as primary prophylaxis for febrile neutropenia when chemotherapy is categorized as high risk (>20% FN risk; see Attachment C).>20% FN risk

Refer to Attachment C for high-risk regimens.

Primary prophylaxis - intermediate risk with risk factors: MGF may be used when chemotherapy is intermediate risk (10–20% FN risk) AND the member has one or more risk factors (age ≥65 years; extensive prior chemotherapy or radiation; persistent/pre-existing neutropenia; bone marrow involvement by tumor; recent surgery and/or open wounds; liver dysfunction with bilirubin >2.0; or renal dysfunction with CrCl <50).10–20% FN risk and ≥1 listed risk factor

Secondary prophylaxis: MGF may be used as secondary prophylaxis for members with solid tumors or non-myeloid malignancies who had a prior episode of febrile neutropenia with the current chemotherapy OR a neutropenic event that led to chemotherapy dose delay or dose decrease in a curative intent setting.

Per NCCN/ASCO guidance secondary prophylaxis recommended when dose reduction or delay would compromise outcomes.

Long-acting MGF restriction: Long-acting MGF (e.g., pegfilgrastim products, eflapegrastim, efbemalenograstim) may be used only if the member is unable to self-administer due to limitations AND unable to travel to the office for daily injections; otherwise short-acting agents are preferred.

Treatment of Febrile Neutropenia

Covered when ALL of the following are met (Treatment of Febrile Neutropenia):

Febrile neutropenia treatment: Member has documented febrile neutropenia per IDSA definition (ANC <1,000 cells/microL AND either a single temperature ≥38.3°C or sustained ≥38.0°C for 1 hour) AND a short-acting MGF (e.g., filgrastim/filgrastim biosimilar/sargramostim) is being used in conjunction with appropriate antibiotic therapy.ANC <1000 and fever criteria per IDSA

Short-acting MGF required for treatment.

Myelodysplastic Syndromes (MDS)

Covered when ALL of the following are met (Myelodysplastic Syndromes):

MDS combination therapy: Short-acting MGF (e.g., filgrastim/filgrastim biosimilar) used in combination with lenalidomide and/or epoetin or darbepoetin alpha in members who have not responded to erythropoietin alone.

MDS for neutropenia/infection prevention: Member has myelodysplastic syndrome (MDS) and is receiving a short-acting MGF for neutropenia and prevention of infections.

Continuation Requests

Continuation requests exemption:

Continuation request criteria: The requested medication was used within the last year AND the member has not experienced disease progression or intolerance to the medication AND no additional medication(s) are being added to the continuation request.

Continuation requests meeting these conditions are exempt from this policy review.

MGF in Members Receiving Concurrent Chemoradiation

Concurrent chemoradiation considerations:

Concurrent chemoradiation: For members receiving concurrent chemoradiation, short-acting MGFs (e.g., filgrastim/filgrastim biosimilar/sargramostim) may be used on a case-by-case basis. If approved, concurrent radiation is recommended to be held during MGF administration.

Long-acting MGFs are excluded in this setting per exclusions.

Covered indications (primary and secondary prophylaxis)

Covered when criteria consistent with guideline-based definitions are met:

Primary prophylaxis for high-risk regimens: Patient is receiving a myelosuppressive anti-cancer regimen categorized as high risk for febrile neutropenia (regimen FN risk >20%; see Attachment C/regimen list) and G-CSF is intended to prevent febrile neutropenia.regimen FN risk >20%

Attachment C lists high-risk regimens.

Secondary prophylaxis after prior FN or dose-limiting event: Patient experienced a prior febrile neutropenic or dose-limiting neutropenic event during a prior chemotherapy cycle (for which primary prophylaxis was not given), and dose reduction or delay would compromise disease-free or overall survival or treatment outcome per NCCN/ASCO guidance.per NCCN/ASCO definitions

Secondary prophylaxis recommended by NCCN and ASCO.

Use of myeloid growth factors (MGFs) with chemotherapy regimens categorized as low febrile neutropenia (FN) risk is generally excluded. Exceptions include members who have previously experienced a dose reduction AND a cycle delay with curative-intent chemotherapy or those with a prior episode of febrile neutropenia on the same regimen. Long-acting MGFs (e.g., pegfilgrastim products, eflapegrastim, efbemalenograstim) are specifically excluded for members receiving concurrent chemoradiation. Additionally, pegfilgrastim/eflapegrastim/efbemalenograstim are not intended for weekly myelosuppressive regimens; short-acting agents (e.g., filgrastim products or sargramostim) should be used in those cases. Requests that exceed stated single-dose limits for long- or short-acting agents are also excluded from coverage.

Primary use of G-CSF for prophylaxis is limited to situations where the chemotherapy regimen carries a clinically significant FN risk (per attachment-based regimen categories) or when guideline-based indications are present. When the regimen’s FN risk is not clinically significant (i.e., low-risk per Attachment A), G-CSF is not indicated unless secondary/exception criteria apply. Secondary prophylaxis is supported per NCCN and ASCO guidance when a prior febrile neutropenic or dose-limiting neutropenic event occurred and a dose reduction or delay would compromise outcomes. Long-acting MGFs are restricted to members unable to self-administer and unable to travel for daily injections; otherwise short-acting MGFs are preferred.

Treatment use of G-CSF is limited to documented febrile neutropenia as defined by IDSA/NCCN criteria (fever plus neutropenia) and should be administered with appropriate antimicrobial therapy. The policy excludes use of MGFs for afebrile neutropenia and does not cover investigational or off-label indications that lack adequate support from FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature.

Primary prophylaxis with MGFs for regimens categorized as low FN risk (see Attachment A) is considered not medically necessary unless the member meets an allowed exception (for example, prior FN on the same regimen or prior dose reduction with cycle delay in curative-intent therapy). Requests for primary prophylaxis without documentation of a guideline-based indication or an allowed exception may be denied as not medically necessary.

Chemotherapy Regimens and FN Risk Categories

Regimen FN risk category	Policy rule for primary prophylaxis	Notes / Attachments
High (>20%)	Primary prophylaxis with a myeloid growth factor (G-CSF) is covered when the member is receiving a chemotherapy regimen categorized as high risk for febrile neutropenia (>20%).	See Attachment C for the list of high-risk drugs/regimens; prior authorization required with regimen risk category documented.
Intermediate (10–20%)	Primary prophylaxis may be covered if the regimen has intermediate FN risk AND the member has one or more specified risk factors (e.g., age ≥65; extensive prior chemo/radiation; persistent neutropenia; bone marrow tumor involvement; recent surgery/open wounds; bilirubin >2.0; CrCl <50).	Policy requires documentation of at least one risk factor; refer to Attachments A–C and clinical documentation expectations for required evidence.
Low (<10%)	Primary prophylaxis with G-CSF is not recommended/considered not medically necessary for low-risk regimens except in specific exceptions (e.g., prior dose reduction and cycle delay with curative intent, or prior febrile neutropenia on the same regimen).	Refer to Attachment A for low-risk regimen list; exceptions must be documented per policy.

Regimen name (as listed in attachments)	Representative regimen components / notes	Regimen FN risk categorization (per attachments)
R-CHOP / R-CHOP variants	Rituximab + Cyclophosphamide + Vincristine + Doxorubicin + Prednisone (and related R-CHOP combinations listed).	Listed in appendix (use to determine FN risk category in Attachments A–C).
HYPER-CVAD ± Rituximab (Cycle A/B)	Alternating high-dose regimens (Hyper-CVAD cycle A and B) with various targeted agents as listed in appendix.	Listed in appendix (use to determine FN risk category).
FOLFIRINOX / modified FOLFIRINOX	Oxaliplatin + Irinotecan + Leucovorin + Fluorouracil (with or without bevacizumab/cetuximab/panitumumab).	Listed in appendix (use to determine FN risk category).
ICE / ICE-based regimens	Ifosfamide + Mesna + Carboplatin + Etoposide (with or without additional agents such as Brentuximab).	Listed in appendix (use to determine FN risk category).
DHAP / R-DHAP / DHAX	Cisplatin + Cytarabine + Dexamethasone (with variations including rituximab or brentuximab).	Listed in appendix (use to determine FN risk category).
CALGB protocols (e.g., CALGB 10403, 8811)	Multiple induction, consolidation, and maintenance combinations (daunorubicin, vincristine, prednisone, pegaspargase, methotrexate, cytarabine, etc.) as listed.	Listed in appendix (use to determine FN risk category).
FOLFOXIRI (± targeted agents)	FOLFOXIRI alone or with bevacizumab/cetuximab/panitumumab as listed in appendix.	Listed in appendix (use to determine FN risk category).
Various multi-agent hematologic and solid tumor regimens (e.g., DHAP, EPOCH, MVAC, GCD, DT-PACE, Tisagenlecleucel supportive regimens)	Extensive list includes numerous lymphoma, leukemia, myeloma, and solid tumor regimens (see Attachments/appendix for full names and combinations).	Listed in appendix (use to determine FN risk category).

Provider Requirements, Prior Authorization, and Denial Risk

Prior Authorization

Prior Authorization Required

Prior authorization is required for myeloid growth factors (MGFs). Evolent is responsible for processing all medication requests from network ordering providers. Medications not authorized by Evolent may be deemed not approvable and therefore not reimbursable.

Evolent must receive and approve prior authorization requests before MGF dispensing.
Medications not authorized by Evolent may be denied and not reimbursed.

Denial Risk

Exclusion-based Denial Triggers

Requests may be denied if they meet any of the exclusion criteria or dosing limits below. Providers should confirm the request meets inclusion criteria and document supporting evidence per accepted references (FDA label, CMS compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature).

Exclusion-based denial triggers include: use with low febrile neutropenia (FN) risk regimens (except specified exceptions), use of long-acting MGF during concurrent chemoradiation, use for FN prevention with CDK4/6 inhibitors, primary prophylaxis with noncytotoxic drugs (except case-by-case), use for afebrile neutropenia, use when member is not receiving myelosuppressive chemotherapy for non-myeloid malignancy or solid tumor, use of pegfilgrastim/eflapegrastim/efbemalenograstim alfa-vuxw with weekly myelosuppressive regimens, use of short-acting filgrastom products within 7 days of a long-acting MGF, use of long-acting MGF in myeloid malignancies or MDS (except specified AML/ALL consolidation), dosing that exceeds single-dose limits, and investigational or off-label uses lacking sufficient evidence.
Specific dosing exclusion thresholds: long-acting MGF single-dose limits — pegfilgrastim products 6 mg, eflapegrastim 13.2 mg, efbemalenograstim alfa-vuxw 20 mg; short-acting filgrastim single-dose limit — 5 mcg/kg/day (rounded to vial sizes: 300 mcg for ≤60 kg or 480 mcg for >60 kg) except for stem cell collection; Leukine (sargramostim) limits — 250 mcg/m2/day (SC) or 500 mcg/m2/day (IV).

Documentation Required

Required Clinical Documentation

Requests for both primary and secondary prophylaxis or treatment must include documentation that supports the indication and regimen risk, and must reference product-specific details per FDA label or package insert.

Required clinical documentation for prophylaxis or treatment requests: diagnosis (type of malignancy), intent of therapy (curative vs palliative), chemotherapy/biotherapy regimen and its FN risk category (reference Attachment A/B/C), prior neutropenic events or documented febrile neutropenia episodes, prior dose reductions or delays attributable to neutropenia, patient-specific risk factors (e.g., age ≥65, prior chemo/radiation, bone marrow involvement, recent surgery/open wounds, hepatic dysfunction with bilirubin >2.0, renal dysfunction with CrCl <50), and whether the member can self-administer or travel for injections when long-acting MGF is requested.
Include relevant lab values (ANC with dates), temperature records if febrile neutropenia is claimed, and supporting citations from FDA label, NCCN or ASCO guidelines, CMS-recognized compendia, or peer-reviewed literature when requesting off-label use.

Step Therapy

Preference and Step for Long- vs Short-acting MGFs

Policy preference favors short-acting MGFs for most settings. Long-acting MGFs are limited to specific circumstances; there is no step-therapy sequence beyond this preference.

Preference and step: Long-acting MGF (e.g., pegfilgrastim and biosimilars, eflapegrastim, efbemalenograstim alfa-vuxw) may be used only when the member is unable to self-administer due to limitations and is unable to travel to the office for daily injections.
Short-acting MGF (e.g., filgrastim and biosimilars, sargramostim) is preferred for treatment of febrile neutropenia and for members on weekly myelosuppressive chemotherapy regimens.

Note

Supporting Evidence and Approval Authority

Use must be supported by authoritative sources. Failure to provide adequate supporting documentation or to meet stated clinical criteria increases the risk of denial.

Supporting evidence accepted: FDA labeling/package insert, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer-reviewed literature per CMS standards.
Utilization Management Department performs review; final approval by the Utilization Management Committee. Non-conforming requests may be denied.

Key Definitions

Febrile neutropenia (IDSA definition)

ANC threshold (IDSA)Absolute neutrophil count (ANC) < 1,000 cells/microL

Fever criteria - single readingSingle temperature ≥ 38.3°C (101°F)

Fever criteria - sustainedTemperature ≥ 38.0°C (100.4°F) sustained for 1 hour

G-CSF prophylaxis (general)

General definitionUse of a G-CSF to prevent febrile neutropenia in a patient receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia

Intended useApplied when regimen FN risk is clinically significant per regimen risk categories (Attachments A–C)

Guideline basisConsistent with NCCN and ASCO recommendations referenced in policy

Secondary prophylaxis

DefinitionAdministration of G-CSF after a febrile neutropenic or dose-limiting neutropenic event during a prior chemotherapy cycle

RationaleRecommended when dose reduction or treatment delay would compromise disease-free or overall survival (per NCCN/ASCO)

Examples of prior eventsPrior febrile neutropenia or neutropenic complication from which prior primary prophylaxis was not received

Febrile neutropenia — alternate definition

Alternate policy temperature thresholdSingle temperature ≥ 38.0°C (100.4°F) in combination with ANC criteria (as used elsewhere in policy: single temp ≥ 38°C for alternate definition)

ANC threshold used in alternate definitionANC ≤ 500 cells/µL, or ANC < 1,000 cells/µL with predicted decline to <500 within 48 hours

ContextThis alternate definition is cited in the policy's Additional Definitions section for febrile neutropenia

Dose-limiting neutropenic event

Core definitionDose-limiting neutropenic event: an event that could impact planned chemotherapy dosing, such as prolonged grade 3 neutropenia (>7 days)

Additional hematologic examplesGrade 3 thrombocytopenia >7 days or grade 4 thrombocytopenia

Includes febrile neutropeniaFebrile neutropenia as defined by guideline criteria is considered a dose-limiting event

Neupogen	filgrastim (brand/product name listed)
Granix	tbo-filgrastim
Leukine	sargramostim
Zarxio	filgrastim-sndz
Nivestym	filgrastim-aafi
Releuko	filgrastim-ayow
Nypozi	filgrastim-txid
Neulasta / Neulasta Onpro Kit	pegfilgrastim
Fulphila	pegfilgrastim-jmdb
Udenyca	pegfilgrastim-cbqv

OpenPayer

Myeloid Growth Factors (MGFs)

Coverage Criteria for Myeloid Growth Factors

Chemotherapy Regimens and FN Risk Categories

Product List and Dosing Limits

Provider Requirements, Prior Authorization, and Denial Risk

Continuation and Line-of-Therapy Rules

Key Definitions

Background on Myeloid Growth Factors