White Blood Cell Growth Factors (G-CSF / GM-CSF) Coverage Criteria
Customize your policy alerts
Sign up for Aloha Care Policy RXMP-06 alerts
Get alerted when Policy RXMP-06 changes without checking for updates manually.
Monitor payer policy activity
Defines prior authorization, step therapy, preferred products, and clinical criteria for coverage of FDA‑approved colony stimulating factors (pegfilgrastim, filgrastim, eflapegrastim, efbemalenograstim, sargramostim) for Aloha Care members, including Medicare/Medicaid guidance.
Added Continuity of Care requirement.
Adopt Optum Health's White Blood Cell Guidelines and changed criteria name.
Updated preferred status.
Colony-Stimulating Factors policy supersedes prior version.
Coverage Criteria for Colony-Stimulating Factors
Bone Marrow/Stem Cell Transplant
Covered when ALL of the following are met
Per product- and indication-specific guidance; see mobilization and transplant sections.
Preferred vs non-preferred rules apply; non-preferred agents require trials of preferred agents per policy.
Documentation should include mobilization regimen details and collection goals when applicable (see provider documentation guidance).
Acute Myeloid Leukemia (AML) induction or consolidation
Covered when ALL of the following are met
Indications supported by randomized trials showing reduced duration of severe neutropenia and faster neutrophil recovery.
Preferred vs non-preferred agent trial requirements apply.
Primary prophylaxis of chemotherapy‑induced febrile neutropenia (FN)
Covered when ALL of the following are met
Chemotherapy regimen incidence based on highest-level trial evidence and CTCAE grading (NCI).
Patient factors used to upgrade intermediate-risk regimens per ASCO/NCCN guidance.
Preferred-agent step therapy rules apply for new starts.
Secondary prophylaxis of febrile neutropenia (FN)
Covered when meeting the following nested logic
Use must align with intended therapy and FDA labeling as applicable.
One of these intents is required.
One of these history items is required to support secondary prophylaxis per policy.
Administrative step therapy condition described in policy.
Secondary prophylaxis of febrile neutropenia
Covered when criteria below are met for listed agents (preferred and non-preferred rules apply):
Secondary prophylaxis general
- Step therapy/agent selection: Preferred agent may be approved if criteria met; non-preferred requires trials of preferred agents (two per drug class if multiple preferred exist; one if only one preferred exists).
Failure to document trials may render request not medically necessary.
- Clinical qualifying scenarios: Member has prior documented neutropenic complication from chemotherapy and dose reduction or delay would compromise disease-free or overall survival; OR member had a neutropenic event on the same regimen despite dose reduction trial; OR primary prophylaxis would otherwise have been indicated for the regimen.prior neutropenic complication
Policy lists these as qualifying circumstances for secondary prophylaxis.
Apply preferred/non-preferred administrative rules.
Treatment of febrile neutropenia
Covered when ALL of the following are met:
Temperature and neutropenia definitions per policy guidance.
High-risk features per policy shortcuts and guideline recommendations.
Use for FN treatment may be denied if long-acting pegfilgrastim given within 14 days.
CSFs should not be used routinely as adjuncts to antibiotics except in high-risk FN per ASCO guidance.
Severe chronic neutropenia (SCN)
Covered when ALL of the following are met:
Per policy definition of SCN.
Documentation should support dosing consistency with labeling.
Transplant, radiation hematopoietic syndrome, and mobilization
Covered when ALL of the following are met depending on indication:
Evidence for ARS indications derives from animal efficacy studies; regulatory ARS indications exist for some agents.
Randomized trials demonstrated shorter duration of severe neutropenia and faster ANC recovery.
Documentation should include timing of apheresis and target collection metrics.
Primary and secondary prophylaxis, mobilization, transplantation, and ARS
Coverage aligns with evidence-based indications and ASCO recommendations; specific clinical scenarios described:
ASCO evidence-based recommendation (strong).
ASCO recommendation; dose reduction may be reasonable alternative in some scenarios.
ASCO strong recommendation.
ASCO guidance.
Choice depends on cancer and transplant type; collection goals should be documented.
ASCO strong recommendation.
Regulatory ARS indications for some agents derive from animal data.
Primary prophylaxis of chemotherapy-induced febrile neutropenia
Covered when ALL of the following are met
Consider alternative regimens not requiring CSF support when available; ASCO recommendation (strong).
Secondary prophylaxis after prior neutropenic complication
Covered when ALL of the following are met
Use when dose reduction or treatment delay would compromise disease-free or overall survival or treatment outcome; dose reduction may be reasonable alternative in many situations.
Required clinical documentation per policy.
Adjunctive CSF use for febrile neutropenia
Covered in specific high-risk situations
ASCO guidance; routine adjunctive use not recommended.
PBSC mobilization and post-transplant support
Covered when appropriate to indication
Typical filgrastim mobilization: 5–24 mcg/kg/day for ~6–7 days with apheresis on days 5–7.
Allogeneic evidence lower strength; recommendation weaker for allogeneic.
Pediatric indications
Covered when ALL of the following are met
CSFs should not be used in pediatric patients with non-relapsed ALL or non-relapsed AML who do not have an infection.
Criteria Short Cuts / Topic mappings
Criteria Short Cuts and topic mappings referenced (but full criteria appear elsewhere in the document).
Full criteria nodes provided in their respective sections.
Medicare coverage follows applicable CMS policy. Review the most current Local Coverage Determination (LCD), National Coverage Determination (NCD), or Local Coverage Article (LCA) that applies to Hawaii when evaluating Medicare Part B requests; the CMS coverage database is the authoritative source. As of 10/19/2025 there was no applicable LCD or NCD identified by this policy. For Medicare Part B new-starts, step therapy requirements must be met in addition to the clinical criteria before approval may be granted.
Requests for colony stimulating factor therapy to treat febrile neutropenia are not eligible for approval when the member has received a long-acting prophylactic pegfilgrastim product within the prior 14 days. This operational exclusion must be documented in the clinical record and will be assessed at authorization.
FDA-approved product indications and dosing are provided for informational context, but FDA approval alone does not establish coverage. Consistent with guideline-based recommendations, CSFs should not be used routinely as an adjunct to antibiotics for febrile neutropenia; consider CSF adjunctive use only for patients with fever and neutropenia who are at high risk for infection-associated complications or who have prognostic factors predictive of poor outcomes.
Routine administration of CSFs for patients with neutropenia who are afebrile is not recommended. For pediatric patients, CSF use is generally guided by clinical protocols: CSFs are reasonable for primary prophylaxis when the child has a high likelihood of febrile neutropenia or to enable dose-intense regimens with demonstrated survival benefit, but CSFs should not be used in pediatric patients with non-relapsed ALL or non-relapsed AML who do not have an infection.
Within the referenced sections there are no additional explicit exclusions beyond those stated elsewhere in the policy. References and bibliographic entries are provided for supporting evidence and product information, but do not introduce additional operational exclusions.
When a non-preferred CSF is requested, the policy requires documented trials of preferred agents before approval. Specifically, the member must have tried and failed two preferred agents from each drug class when multiple preferred options exist; if only one preferred agent exists in a class, a single preferred-agent trial is required. This step-therapy requirement applies to new starts and must be documented for prior authorization.
Failure to document required prior trials of preferred agents for non-preferred CSFs may render the request not medically necessary under the policy's step therapy rules. The policy expects documentation that preferred-agent trials were attempted and either failed or were not tolerated, or that a contraindication exists, before a non-preferred product is authorized.
Operationally, the policy states that routine use of CSFs for afebrile neutropenia is not supported. Requests for CSFs to treat afebrile neutropenia should include a clear rationale tied to high-risk clinical features or protocol-driven indications; otherwise they are generally not consistent with the guideline-based recommendations cited in this policy.
Because routine adjunctive use of CSFs with antibiotics for febrile neutropenia is not recommended, such requests should include documentation of high-risk features or poor prognostic indicators to justify therapy. FDA labeling is informational only and does not, by itself, establish medical necessity for adjunctive CSF use.
Some document sections contain references and mapping notes but do not state explicit 'not medically necessary' determinations beyond the policy's general guidance. Absence of an explicit NMN statement in a referenced chunk does not override the policy rules that apply elsewhere (for example, step therapy or routine-use guidance).
Applicable Codes, Thresholds, and Key Definitions
| 96377 | Application of on-body injector (includes cannula insertion) for timed subcutaneous injection [Neulasta OnPro injector] |
| J2506 | Injection, pegfilgrastim, excludes biosimilar, 0.5 mg (Neulasta) |
| Q5111 | Injection, pegfilgrastim, excludes biosimilar, 0.5 mg (Neulasta) (alternate code listed) |
| Q5120 | Injection, pegfilgrastim-cbqv, biosimilar, (Udenyca), 0.5 mg |
| Q5122 | Injection, pegfilgrastim-bmez, biosimilar, (Ziextenzo), 0.5 mg |
| Q5108 | Injection, pegfilgrastim-apgf, biosimilar, (Nyvepria), 0.5 mg |
| Q5127 | Injection, pegfilgrastim-jmdb, biosimilar, (Fulphila), 0.5 mg |
| Q5130 | Injection, pegfilgrastim-fpgk (Stimufend), biosimilar, 0.5 mg |
| Q5130 | Injection, pegfilgrastim-pbbk (Fylnetra), biosimilar, 0.5 mg |
| J1442 | Injection, filgrastim (G-CSF), excludes biosimilars, 1 microgram (Neupogen) |
| Fulphila (pegfilgrastim-jmdb) | pegfilgrastim biosimilar product listed as indicated for FN prophylaxis |
| Fylnetra (pegfilgrastim-pbbk) | pegfilgrastim biosimilar indicated for FN prophylaxis |
| Granix (tbo-filgrastim) | tbo-filgrastim indicated to reduce duration of severe neutropenia |
| Leukine (sargramostim) | GM-CSF indicated for multiple uses including AML post-induction, mobilization, transplant recovery, and ARS |
| Neulasta (pegfilgrastim) | pegfilgrastim indicated for FN prophylaxis and ARS survival |
| Neupogen (filgrastim) | filgrastim indicated for FN prophylaxis, AML recovery, BMT support, mobilization, congenital neutropenias, and ARS |
| Nivestym (filgrastim-aafi) | filgrastim biosimilar with indications similar to filgrastim |
| Nyvepria (pegfilgrastim-apgf) | pegfilgrastim indicated for FN prophylaxis |
| Releuko (filgrastim-ayow) | filgrastim biosimilar indicated for FN prophylaxis and other filgrastim indications |
| Rolvedon | pegfilgrastim product indicated for FN prophylaxis |
| C9399 | Unclassified drugs or biologics |
| 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 |
| Q5101 | Injection, filgrastim-sndz, biosimilar (Zarxio), 1 microgram |
| Q5111 | Injection, pegfilgrastim-cbqv, biosimilar, (Udenyca), 0.5 mg |
| Q5120 | Injection, pegfilgrastim-bmez, biosimilar, (Ziextenzo), 0.5 mg |
| Q5122 | Injection, pegfilgrastim-apgf, biosimilar, (Nyvepria), 0.5 mg |
| Q5125 | Injection, filgrastim-ayow, biosimilar, (Releuko), 1 microgram |
| Q5127 | Injection, pegfilgrastim-fpgk, biosimilar, (Stimufend), 0.5 mg |
| Q5130 | Injection, pegfilgrastim-pbbk, biosimilar, (Fylnetra), 0.5 mg |
| No codes listed |
Prior Authorization, Documentation, and Step Therapy Requirements
Prior authorization required for listed CSF products
Prior authorization (PA) is required for listed CSF products for both medical and pharmacy benefits; approvals may be issued for up to one year. Submit PA requests referencing the specific HCPCS/J/Q code or on-body injector (96377) and the clinical indication.
- PA applies to medical and pharmacy benefits for listed HCPCS/J/Q codes and the on-body injector (96377).
- Approval durations: up to 1 year.
Prior authorization for non-preferred agents
Prior authorization is required for non-preferred growth factor agents unless the member has tried the required preferred agents or meets documented exception criteria; criteria differ by indication (e.g., secondary prophylaxis vs treatment of FN).
- Non-preferred requests require documentation that the member tried and failed preferred agents as specified by the policy.
- Indication-specific rules (secondary prophylaxis vs treatment) affect PA requirements.
Prior authorization for CSF agents and indications
Prior authorization is expected for the CSF agents and indications listed (pegfilgrastim products, filgrastim products, sargramostim, eflapegrastim, efbemalenograstim) where coverage is contingent on meeting clinical criteria; include the drug name and indication in the request.
- List of covered/recognized agents (e.g., Neulasta, Neupogen, Leukine, Fulphila, Rolvedon, Ryzneuta) appears in the document.
- Coverage for these agents is contingent on meeting the policy's clinical criteria for the stated indication.
Prior authorization for listed CSF HCPCS/J-codes
Submit prior authorization requests for CSF agents using the listed HCPCS/J- and Q-codes and include clinical justification referencing the indication (e.g., primary prophylaxis when FN risk ≈20% or higher, secondary prophylaxis after prior neutropenic complication, mobilization, or post‑transplant support).
- Include the HCPCS/J- or Q-code and clinical indication when requesting authorization.
- Primary prophylaxis should reference FN risk (~20% threshold) when applicable; secondary prophylaxis should reference prior neutropenic events or intent.
Prior authorization requirement (change history noted)
The policy's change history documents adoption of external guidelines and a continuity-of-care requirement, but this section does not specify additional PA procedural steps beyond standard authorization submission.
- Change History notes: Added Continuity of Care requirement and adoption of Optum Health White Blood Cell Guidelines.
- No new specific PA workflow steps are specified in the change-history excerpt.
Step therapy for new starts — document inadequate response/intolerance/contraindication
For new starts, step therapy requires documentation of inadequate response, intolerance, or contraindication to the specified preferred agents before a non-preferred long‑ or short‑acting agent may be approved.
- Long-acting agents: member must have inadequate response/intolerance/contraindication to Neulasta or Udenyca for new starts.
- Short-acting agents: member must have inadequate response/intolerance/contraindication to Zarxio or Nivestym for new starts.
Preferred-agent trial required for non-preferred agents
When requesting a non-preferred agent, document prior trials and failures of preferred agents per policy: generally two preferred agents from each drug class are required when multiple preferred options exist; if only one preferred exists, one trial is sufficient.
- Preferred-agent trials must be documented (try/fail) for non-preferred approvals.
- If only one preferred agent exists, only one prior trial is required.
Preferred agent selection considerations
When selecting a preferred agent, consider convenience, cost, and clinical situation; the policy endorses therapeutic equivalence among granulocyte CSFs and lists pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim biosimilars as preferred choices where applicable.
- Policy notes therapeutic equivalence among granulocyte CSFs and GM‑CSF comparison unchanged since 2006.
- Choice among agents may be guided by convenience and cost considerations.
Operational note — send ADRC referral with chart notes for QUEST & non-ABD members
Pharmacy staff: for QUEST and non-ABD members with cancer, send an ADRC referral accompanied by chart notes to support the request.
- Include relevant chart notes when sending ADRC referral.
Required clinical documentation — diagnosis
Document the clinical diagnosis to support PA requests — examples include febrile neutropenia (FN), severe chronic neutropenia (SCN) with ANC ≤ 500/mcL, or hematopoietic syndrome from acute radiation exposure.
- For SCN, document chronic ANC ≤ 500 neutrophils/mcL.
- For radiation syndrome, document acute exposure and FDA‑label dosing intent.
Mobilization and collection documentation
For mobilization and collection, include regimen details (drug, dose, route, duration), timing of apheresis relative to dosing, target collection goals (e.g., MNC or CD34+ thresholds), and the number of apheresis procedures performed.
- Document filgrastim dosing/timing (e.g., 6–7 days with apheresis on days 5–7; doses 10–24 mcg/kg/day) when used for PBPC mobilization.
- Document target MNC/CD34+ collection goals and number of aphereses (e.g., 5–8 procedures) per cohort expectations.
Required clinical lab and vital sign documentation
Include relevant clinical labs and vital signs: ANC values (neutropenia <1,500/µL; severe neutropenia <500/µL) and temperature recordings when FN is claimed (single oral temperature ≥38.3°C or ≥38.0°C for >1 hour).
- Record ANC with dates and trend if predicting decline to ≤500/µL within 48 hours when applicable.
- Include temperature documentation meeting FN definition when requesting treatment-related CSF.
Secondary prophylaxis justification — document prior neutropenic events and rationale
For secondary prophylaxis requests, document the prior neutropenic complication (e.g., febrile neutropenia or neutropenia that caused a treatment delay), any chemotherapy dose reductions or delays, and a rationale explaining why dose reduction or delay would compromise disease‑free or overall survival.
- Specify the prior cycle(s) with neutropenic complication and consequences (dose delay/reduction).
- Explain why alternative measures (dose reduction/delay) would jeopardize treatment outcome.
Documentation and supporting references — cite package inserts and guidelines
Include supporting references and product information where relevant: package inserts and guideline citations (e.g., Granix, Zarxio, Nivestym, Fulphila, Udenyca, Ziextenzo, Nyvepria, Releuko, Fylnetra, Rolvedon, Ryzneuta; NCCN, ASCO, EORTC, IDSA, CDC) that substantiate indication, regimen, and dosing.
- Cite specific package inserts or guideline documents in the clinical rationale when appropriate.
- Use ASCO/NCCN recommendations to support prophylaxis thresholds and clinical decision‑making.
Denial risk — Medicare Part B new-start step therapy not met
Medicare Part B new‑start step therapy criteria must be met for applicable members; requests may be denied if documentation does not show inadequate response, intolerance, or contraindication to required preferred agents.
- For Medicare Part B new starts, step therapy for long‑ and short‑acting agents requires documented inadequate response/intolerance/contraindication to listed preferred agents.
- PA is required in addition to meeting step therapy and clinical criteria.
Denial risk — failure to document prior preferred-agent trials
If the provider does not document prior trials and failures of required preferred agents when prescribing a non‑preferred agent, the request may be denied as not meeting step therapy/prior‑trial requirements.
- Document prior preferred-agent trials and outcomes (failure, intolerance) when requesting non-preferred agents.
- Policy requires two failed preferred agents per drug class when multiple preferred options exist.
Denial risk — recent long-acting pegfilgrastim within 14 days
Treatment of febrile neutropenia may be denied if the member received long‑acting prophylactic pegfilgrastim within the prior 14 days; confirm timing of any recent long‑acting pegfilgrastim in the chart.
- Verify and document that the member has not received long‑acting prophylactic pegfilgrastim in the previous 14 days when requesting CSF for FN treatment.
- Requests citing recent prophylactic long‑acting pegfilgrastim may be excluded.
Denial risk — primary prophylaxis below ~20% FN risk
Requests for primary CSF prophylaxis when the patient's overall risk of febrile neutropenia is below approximately 20% may be denied for not meeting primary prophylaxis criteria; include documented FN risk assessment if requesting primary prophylaxis near this threshold.
- Policy applies an ~20% FN risk threshold for routine primary prophylaxis initiation.
- For intermediate‑risk regimens (10–20%), document patient risk factors that justify primary prophylaxis.
Denial risk — dose-dense regimen justification required
Use of dose‑dense chemotherapy regimens with CSF support must be supported by convincing efficacy data; requests for dose‑dense regimens without evidence of benefit (outside supported indications such as adjuvant high‑risk breast cancer or high‑intensity MVAC for urothelial cancer) may not meet authorization criteria.
- Dose‑dense regimens require evidence of survival or meaningful efficacy benefit to justify CSF support.
- Document trial data or guideline support when requesting CSF for dose‑dense regimens outside well-supported indications.
Chemotherapy Regimens, Dosing, and Supported Indications
| Regimen / Context | Coverage status | Notes / Criteria |
|---|---|---|
| Dose-dense AC → paclitaxel (breast cancer) | ||
| Dose-dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) (bladder cancer) | ||
| Other chemotherapy regimens with FN incidence based on highest-level trial evidence |
| Regimen / Agents | Coverage status | Indication / Notes |
|---|---|---|
| Fludarabine + cytarabine ± idarubicin | ||
| Cladribine + cytarabine ± mitoxantrone or idarubicin | ||
| Use in induction or consolidation for AML and specified relapsed/refractory regimens |
| Agent / Dosing (trial-reported) | Route / Timing | Context / Notes |
|---|---|---|
| Filgrastim 5 mcg/kg/day | ||
| Subcutaneous; started 24 hours after last chemotherapy dose in AML randomized trial | ||
| Reduced duration of severe neutropenia and time to neutrophil recovery (AML induction/consolidation) |
| Agent / Dose range | Mobilization timing / apheresis | Post-reinfusion / Engraftment notes |
|---|---|---|
| Filgrastim 5–24 mcg/kg/day (commonly 10–24 mcg/kg/day for mobilization) | ||
| Administered ~6–7 days with apheresis commonly on days 5–7 | ||
| Continue filgrastim after reinfusion until sustained ANC ≥ 500/mm3 as described in trials |
| Regimen / Setting | Coverage status | Evidence / Notes |
|---|---|---|
| Dose-dense chemotherapy with CSF support (adjuvant high-risk breast cancer) | ||
| Use of CSF support for dose-dense regimens only when convincing efficacy data exist or within clinical trials | ||
| ASCO/NCCN–supported for adjuvant high-risk breast cancer (evidence quality: high) |
| Regimen | Coverage status | Notes / Evidence |
|---|---|---|
| High-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) with CSF support (urothelial cancer) | ||
| CSF support indicated when regimen is high-dose intensity MVAC | ||
| Efficacy data support use in this urothelial cancer setting (evidence quality: intermediate to high) |
| Regimen / Setting | Coverage status | Rationale / Guidance |
|---|---|---|
| Dose-dense regimens in non-Hodgkin lymphoma | ||
| Limited and conflicting data; not routinely recommended | ||
| Policy advises against routine use unless within an appropriately designed clinical trial |
| Topic / Reference | Coverage status | Notes |
|---|---|---|
| Use after autologous bone marrow transplantation | ||
| Prevention of FN in chemotherapy for breast cancer (pegfilgrastim trial cited) | ||
| Documented references include randomized trials and multiple product inserts cited in reference list |
Background and Definitions
Colony stimulating factors include granulocyte colony-stimulating factors (G-CSFs) such as filgrastim and pegfilgrastim and granulocyte–macrophage CSF (GM‑CSF) agents such as sargramostim. These agents are used to prevent or treat chemotherapy-induced febrile neutropenia, to mobilize hematopoietic progenitor cells for peripheral blood collection, to shorten duration of severe neutropenia after autologous stem-cell transplantation, and to treat hematopoietic syndrome following radiation exposure where regulatory approvals derive from animal efficacy data. Clinical guidance supports primary prophylaxis when the overall risk of febrile neutropenia is approximately 20% or higher, secondary prophylaxis after a prior neutropenic complication when dose reduction or delay would compromise outcomes, mobilization regimens (e.g., filgrastim courses with apheresis on days 5–7 or sargramostim 250 mcg/m2/day in trial contexts), and restricted pediatric and post-transplant uses per protocol or evidence strength.
Line of Therapy Designations
first-line
Line-of-therapy mapping per coverage sections.
varied
See individual criterion sections for line-of-therapy detail.
second-line
Manufacturer indication supports this line-of-therapy mapping.
first-line
Product indications are informational; apply ASCO/NCCN criteria for prophylaxis.
first-line
Dose-dense regimens require convincing efficacy data per recommendations.
first-line
Short-cut mappings reference full criteria elsewhere.
Policy Change History
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.