HIGHMARK COMMERCIAL MEDICAL POLICY - PENNSYLVANIA

 
 
Medical Policy:
I-214-009
Topic:
Luspatercept (Reblozyl)
Section:
Injections
Effective Date:
May 1, 2026
Issued Date:
May 1, 2026
Last Revision Date:
April 2026
Annual Review:
April 2026
 
 

Luspatercept-aamt (Reblozyl®) is a recombinant fusion protein that binds several endogenous TGF-β superfamily ligands, which diminishes Smad2/3 signaling. Luspatercept-aamt (Reblozyl) promotes maturation through differentiation of late-stage erythroid precursors (normoblasts). In a model of β-thalassemia, luspatercept-aamt (Reblozyl) decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis.

Luspatercept-aamt (Reblozyl) increases risk of thromboembolic events (TEE). Individuals should reduce modifiable risk factors (e.g., smoking, use of oral contraceptives). Thromboprophylaxis should be considered in individuals with beta thalassemia at increased risk of TEEs. Luspatercept-aamt (Reblozyl) may cause an increase in blood pressure. 

Policy Position

Luspatercept-aamt (Reblozyl) may be considered medically necessary for individuals who meets the criteria for ANY ONE of the following indications:

Anemia due to Beta Thalassemia

  • Luspatercept-aamt (Reblozyl) is being prescribed by or in consultation with a hematologist or other specialist with expertise in the diagnosis and management of beta thalassemia; and
  • Individual is 18 years of age or older; and
  • Individual diagnosed with anemia due to beta thalassemia; and
  • Individual is not diagnosed with hemoglobin S/β-thalassemia or alpha-thalassemia; and
  • Hemoglobin (Hgb) level is less than or equal to 11 g/dL; and
  • Individual requires regular red blood cell (RBC) transfusions (i.e. at least six (6) or more RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period); and
  • Luspatercept-aamt (Reblozyl) is not being used as a substitute for RBC transfusions in individuals who require immediate correction of anemia; and
  • Individual is not concomitantly being treated with erythropoiesis stimulating agents (ESA), immunosuppressants, or hydroxyurea; and
  • Individual has not received gene therapy or if individual has received gene therapy the individual meets the above criteria for regular RBC transfusions along with all other criteria; and
  • Individual is not concomitantly enrolled in a clinical trial for gene therapy for beta thalassemia; and
  • Initial authorization will be for up to six (6) months; or

Reauthorization Criteria

Reauthorization of luspatercept-aamt (Reblozyl) for a period of 12 months may be considered medically necessary for individuals who meet ALL of the following criteria:

  • Individual diagnosed with ANY ONE of the above diagnoses; and
  • Prescribed by or in consultation with a hematologist, or other specialist with expertise in the diagnosis and management of beta thalassemia; and
  • Previously met the initial authorization criteria; and
  • Individual experiences a decrease in transfusions; and
  • If individual experiences a response followed by a lack of response or lost response to luspatercept-aamt (Reblozyl), a typical cause was found and resolved or if no typical cause a dose increase resulted in a continued response; and
  • Reauthorization will be for up to 12 months.

Luspatercept-aamt (Reblozyl) not meeting the criteria as indicated in this policy is considered not medically necessary.

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NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits. 

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NOTE: luspatercept-aamt (Reblozyl) is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

References

1.     Reblozyl® (luspatercept-aamt) injection, for subcutaneous use [package insert]. Celgene Corporation. Summit, NJ. Revised 02/2026.

2.     Piga A, Perrotta S, Gamberini MR, et al. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia. Blood. 2019;133(12):12791289.

3.     Clinical PharmacologyTM Compendium. 2026. Tampa FL: Gold Standard, Inc. Luspatercept.

4.     Micromedex DrugDex Compendium®. 2026. Luspatercept.

5.     Fenaux P, Platzbecker GJ , Mufti G, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. NEJM. 2020;382:140-51.

6.     Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. NEJM. 2020;382:1219-31.

7.     Luspatercept-aamt In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated May 10, 2024.

8.     National Comprehensive Cancer Network (NCCN). Drugs and Biologics Compendium®. 2026. Luspatercept-aamt.

9.     Platzbecker U, Della Porta MG, Zeidan AM, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10399):p373-385.

Related Policies

Refer to Evolent Policy ECG 3161 Reblozyl (luspatercept-aamt) for additional information. 


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Place of Service: Outpatient

The administration of luspatercept-aamt (Reblozyl) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of insured business and, if elected, ASO.



Links





This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical or other circumstances may warrant individual consideration, based on review of applicable medical records, as well as other regulatory, contractual and/or legal requirements.

Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:

  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
    • Qualified sign language interpreters
    • Written information in other formats (large print, audio, accessible electronic formats, other formats)
  • Provides free language services to people whose primary language is not English, such as:
    • Qualified interpreters
    • Information written in other languages

If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

This information is issued by Highmark Blue Shield on behalf of its affiliated Blue companies, which are independent licensees of the Blue Cross Blue Shield Association.  Highmark Inc. d/b/a Highmark Blue Shield and certain of its affiliated Blue companies serve Blue Shield members in the 21 counties of central Pennsylvania. As a partner in joint operating agreements, Highmark Blue Shield also provides services in conjunction with a separate health plan in southeastern Pennsylvania.  Highmark Inc. or certain of its affiliated Blue companies also serve Blue Cross Blue Shield members in 29 counties in western Pennsylvania, 13 counties in northeastern Pennsylvania, the state of West Virginia plus Washington County, Ohio, the state of Delaware[ and [8] counties in western New York and Blue Shield members in [13] counties in northeastern New York].  All references to Highmark in this document are references to Highmark Inc. d/b/a Highmark Blue Shield and/or to one or more of its affiliated Blue companies.




Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:

  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
  • Qualified sign language interpreters
  • Written information in other formats (large print, audio, accessible electronic formats, other formats)

  • Provides free language services to people whose primary language is not English, such as:
  • Qualified interpreters
  • Information written in other languages
    • If you need these services, contact the Civil Rights Coordinator.

    If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295 , TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

    You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

    U.S. Department of Health and Human Services
    200 Independence Avenue, SW
    Room 509F, HHH Building
    Washington, D.C. 20201
    1-800-368-1019, 800-537-7697 (TDD)

    Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.