Colony Stimulating Factors
Customize your policy alerts
Sign up for Blue Cross Blue Shield - Iowa Policy 05.02.41 alerts
Get alerted when Policy 05.02.41 changes without checking for updates manually.
Monitor payer policy activity
Defines preferred short- and long-acting colony stimulating factor (CSF) products, exception criteria, documentation and prior authorization requirements for coverage, and clinical criteria for initial and continuation approval for selected products (notably Rolvedon). Affects prescribers and members under Blue Cross Blue Shield - Iowa benefit plans.
No material clinical or coverage changes in this revision.
Coverage Criteria
Exception Criteria for Targeted Products
Coverage of targeted (non-preferred) short- and long-acting products is provided when specific exception criteria are met
Approval will be for 6 months
Policy note: for Rolvedon, member must meet BOTH the Rolvedon exception criteria and the Initial Approval/Continuation criteria when applicable.
Initial Approval — Prevention of Febrile Neutropenia
Prevention of neutropenia in cancer patients receiving myelosuppressive chemotherapy — Initial Approval criteria (applies to Rolvedon referenced explicitly)
Other Indications
Other indications eligible for authorization
Continuation Therapy
Continuation of Therapy
General coverage criteria
Coverage is guided by chemotherapy regimen FN risk and patient risk factors
Appendices provide examples of regimens with >20% and 10–20% FN risk; Appendix C lists patient risk factors (e.g., age ≥65, bone marrow involvement, prior chemo/radiation, active infection, poor nutrition, poor performance status, previous FN, significant comorbidities, persistent neutropenia).
This policy may not apply to members covered under the Federal Employee Program (FEP). Benefits and coverage determinations for FEP members are governed separately from this policy; providers should verify FEP benefit administration prior to relying on the exception and prior authorization processes described here.
Appendices A–G and the regimen listings in this policy are provided as examples of chemotherapy regimens associated with intermediate or high risk of febrile neutropenia and are not comprehensive. Clinical judgment and current guideline sources should be used when assessing regimen risk; patient-level risk factors (see Appendix C) also modify the need for colony stimulating factor prophylaxis.
If a patient does not meet the specified initial authorization or continuation criteria for Rolvedon, coverage is not considered medically necessary. Continuation requests (including those for new members) must satisfy all initial authorization requirements; failure to do so will render Rolvedon ineligible for coverage under this policy.
Initial Therapy Criteria
Initial Therapy — Rolvedon
Initial approval rules for Rolvedon
Initial therapy considerations
Initial use guided by chemotherapy FN risk and patient risk factors.
Appendices list selected regimens and Appendix C lists patient risk factors.
Continuation of Therapy
Continuation of Therapy
Continuation requirements
Step Therapy and Product Trial Requirements
| Requirement | Details |
|---|---|
| Step requirement | Member must have failed treatment with all preferred products due to a documented intolerable adverse event not attributable to the active ingredient, or have a documented latex allergy requiring latex-free vials with documented inadequate response or intolerable effect to Nivestym. (Approval will be for 6 months.) |
| Applies to targeted short-acting products | Targeted short-acting products (Neupogen, Filkri, Granix, Nypozi, Releuko) are covered when one of the listed exception criteria is met (failure of preferred products or latex allergy with inadequate response to Nivestym). |
| Applies to targeted long-acting products | Targeted long-acting products (Armlupeg, Fylnetra, Nyvepria, Stimufend, Udenyca, Udenyca Onbody, Ziextenzo) are covered when the member has failed all preferred long-acting products due to documented intolerable adverse effects. Rolvedon and Ryzneuta require documented inadequate response or intolerable adverse effect to any preferred products; Rolvedon also must meet initial/continuation criteria when applicable. |
| Agent group | Listed agents / codes |
|---|---|
| Preferred short-acting (examples) | Nivestym, Zarxio (preferred short-acting biosimilars) — see HCPCS/CPT/Q codes list; Neupogen (J1442) listed as reference product. |
| Targeted short-acting | Neupogen (J1442), Filkri, Granix (J1447), Nypozi (C9173/Q5148), Releuko (Q5125) — multiple filgrastim products listed in procedures and billing codes and package insert references. |
| Preferred/Referenced long-acting (examples) | Neulasta and biosimilars (Fulphila Q5108, Udenyca Q5111, Ziextenzo Q5120, Nyvepria Q5122, Fylnetra Q5130, Stimufend Q5127, etc.) — listed by Q-codes in billing codes. |
| Targeted long-acting | Armlupeg, Fylnetra (Q5130), Nyvepria (Q5122), Stimufend (Q5127), Udenyca (Q5111), Udenyca Onbody, Ziextenzo (Q5120) — policy lists multiple reference biologics and biosimilars; no explicit sequence or step order is specified. |
Coding
| C9399 | Unclassified drugs or biologicals |
| C9173 | Injection, filgrastim-txid (Nypozi), biosimilar, 1 microgram (cancelled 7/1/2025) |
| J1442 | Injection, filgrastim (g-csf), excludes biosimilars, 1 microgram (Neupogen) |
| J1447 | Injection, tbo-filgrastim, 1 mcg |
| J1449 | Injection, eflapegrastim-xnst, (Rolvedon) 0.1 mg (effective 4/1/2023) |
| J2820 | Injection, sargramostim (gm-csf), 50 micrograms (Leukine) |
| J3590 | Unclassified biologicals |
| J9361 | Injection, efbemalenograstim alfa-vuxw, 0.5 mg (Ryzneuta) |
| Q5108 | Injection, pegfilgrastim-jmdb, biosimilar, (Fulphila), 0.5mg |
| Q5111 | Injection, pegfilgrastim-cbqv, biosimilar, (Udenyca), 0.5mg |
Provider Actions & Documentation
Prior authorization required for non-preferred (targeted) CSF products; exceptions considered
Prior authorization is required for coverage of non-preferred (targeted) colony stimulating factor products. Exceptions for targeted short- and long-acting agents are considered when the member meets the policy’s exception criteria (for example, documented failure of all preferred products due to an intolerable adverse event or documented latex allergy with need for latex-free vials). Approval for targeted short-acting agents is generally granted for 6 months where exception criteria are met.
- Targeted short-acting exceptions: documented failure of all preferred products due to intolerable adverse event OR documented latex allergy requiring latex-free vials plus inadequate response/intolerable effect to Nivestym.
- Leukine: documented inadequate response/intolerable adverse effect to any preferred product OR requested for uveal melanoma with immunoembolization.
- Targeted long-acting exceptions: documented failure of all preferred long-acting products due to documented intolerable adverse effect.
- Rolvedon/Ryzneuta: documented inadequate response or intolerable adverse effect to any preferred products.
- Approval duration for targeted short-acting products: 6 months (where specified).
Report claims with listed HCPCS/CPT/Q-codes; prior authorization may be required
Submit claims and prior authorization requests using the HCPCS/CPT/Q-codes listed in the policy; prior authorization may be required per payer processes for the listed codes and products.
Targeted product coverage requires failure or inadequate response to all preferred products
Coverage of targeted (non-preferred) products generally requires documented failure, inadequate response, or intolerable adverse effect to all preferred products (short- and long-acting) before an exception is granted for the targeted agent.
- Failure must be documented as intolerable adverse event not attributable to the active ingredient per prescribing information, or documented inadequate response as specified for particular agents.
- For Leukine, Rolvedon, and Ryzneuta the policy requires documented inadequate response or intolerable adverse effect to any preferred products.
Policy lists multiple reference biologics and biosimilars; no explicit step sequence provided
The policy lists multiple reference biologics and biosimilars by HCPCS/Q-code and package insert; no explicit step-sequence algorithm among listed biosimilars/reference products is provided.
- Multiple pegfilgrastim and filgrastim biosimilars and reference products are listed with Q- and J-codes and package insert citations.
- No hierarchy or required trial order among the listed biosimilars/reference biologics is specified in the policy text.
Document diagnosis, chemotherapy regimen; add patient risk factors for intermediate-risk regimens
For primary prophylaxis requests, provide documentation of the member’s diagnosis and the specific chemotherapeutic regimen; if the regimen confers intermediate FN risk (10–19%), also provide documentation of patient risk factors confirming high risk for febrile neutropenia.
- Required: member diagnosis and chemotherapeutic regimen.
- If regimen FN risk is 10–19% (see Appendix B), document patient risk factors (Appendix C) that confer high risk for febrile neutropenia.
Report services with appropriate CPT/HCPCS (listed J- and Q-codes), revenue and ICD codes
Providers must report services using appropriate CPT, HCPCS (including the policy’s listed J- and Q-codes), revenue and ICD diagnostic codes; package insert and guideline references in the policy support the clinical rationale.
- Include the applicable J- and Q-codes from the policy’s code list when submitting claims or prior authorization requests.
- Use appropriate revenue codes and ICD diagnosis codes corresponding to the indication being treated.
Rolvedon considered not medically necessary when authorization criteria are not met
If the member does not meet the policy’s initial authorization criteria for Rolvedon (and continuation criteria for ongoing use), Rolvedon is considered not medically necessary and should not be approved.
- Continuation requests (including new members) must meet all initial authorization criteria; lack of meeting criteria renders Rolvedon not medically necessary.
Using unlisted codes (C9399, J3590) or non-listed drug codes may trigger billing/coverage issues
Do not submit claims using unlisted drug/biologic codes (C9399, J3590) or codes that do not represent the drug being administered; use of unlisted codes or drugs not represented by the listed HCPCS/CPT/Q-codes may trigger billing or coverage review.
Background
Colony stimulating factors (short- and long-acting) are used to prevent or treat neutropenia associated with myelosuppressive chemotherapy and related clinical scenarios (including stem cell transplantation and certain hematologic conditions). Primary prophylaxis is indicated when the chemotherapy regimen confers a high risk (>20%) of febrile neutropenia, and may be considered for intermediate-risk (10–20%) regimens when patient-specific risk factors are present; patient factors (e.g., age ≥65, active infection, bone marrow involvement) modify the decision to initiate therapy. The policy references regimen appendices and requires documentation of diagnosis and chemotherapy to support authorization.
Definitions
Site of Care
No site‑of‑care restriction specified for infusion center in this policy excerpt
The policy provides no specific site‑of‑care restrictions for infusion centers in the cited sections; no site‑of‑care action is required based on these chunks.
- Providers should follow usual facility billing practices; no additional payer site‑of‑care rule is specified in these sections.
Biosimilar & Reference Product Information
Preferred short‑acting filgrastim: Nivestym and Zarxio; Neupogen targeted
Nivestym and Zarxio are the preferred short‑acting filgrastim products; Neupogen and other targeted filgrastim products require meeting the policy’s exception criteria for coverage.
- Preferred short‑acting products: Nivestym (filgrastim‑aafi) and Zarxio (filgrastim‑sndz).
- Targeted short‑acting agents (Neupogen, Filkri, Granix, Nypozi, Releuko) require exception documentation per policy.
Preferred short‑acting products (Nivestym, Zarxio)
The policy explicitly lists Nivestym and Zarxio as the preferred short‑acting products (filgrastim biosimilars) to be used prior to exception requests for targeted filgrastim agents.
- Use preferred agents Nivestym or Zarxio when clinically appropriate to avoid prior authorization for targeted agents.
Neulasta and pegfilgrastim biosimilars listed by Q‑code
Pegfilgrastim (Neulasta) and multiple pegfilgrastim biosimilars are listed by Q‑code with package insert references; the policy references both reference biologics and biosimilars without stating an explicit preference among them in the cited sections.
Neulasta listed among pegfilgrastim products; no hierarchy provided
Neulasta is included among the listed pegfilgrastim products and biosimilars; the cited sections do not provide a hierarchy or explicit preference within the pegfilgrastim group.
- Neulasta and its biosimilars are enumerated with package insert citations; no ordering or step sequence is provided in these chunks.
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.