Reblozyl (luspatercept-aamt)

POLICY NUMBER

L.5.01.552

Reblozyl (luspatercept-aamt)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Beta thalassemia is a rare hereditary disorder characterized by reduced hemoglobin production, which results in a decrease in oxygen transported to cells throughout the body. Supportive treatment for people with beta thalassemia often consists of lifelong regimens of chronic blood transfusions for survival as well as treatment for iron overload due to the transfusions. People with beta thalassemia are also at an increased risk of developing abnormal blood clots.

Reblozyl (luspatercept-aamt) is a recombinant fusion protein indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions, for the treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular RBC transfusions, and for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). Luspatercept induces erythroid maturation by binding several endogenous TGF-β superfamily ligands, thus diminishing Smad2/3 signaling, which is thought to improve hematology parameters associated with ineffective erythropoiesis in beta thalassemia.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Initial Evaluation

Reblozyl (luspatercept-aamt) may be considered medically necessary when ALL of the following criteria are met:

1. Individual is ≥18 years of age;

2. ONE of the following:

   1. Individual has a confirmed diagnosis of β-thalassemia, excluding S/β-thalassemia and alpha-thalassemia variants, and ALL of the following:

      1. Individual requires regular red blood cell (RBC) transfusions as defined by BOTH of the following:

         1. Individual required ≥6 RBC units in the previous 24 weeks; AND

         2. There was no transfusion-free period >35 days in the previous 24 weeks; 

      2. Pre-dose hemoglobin level (or pretransfusion hemoglobin level if an RBC transfusion just occurred) is ≤11 g/dL; AND

      3. Individual does not have major organ damage (e.g., liver disease with ALT>3x ULN, heart disease, heart failure NYHA classification 3or higher, recent myocardial infarction within 6 months of treatment), clinically significant pulmonary fibrosis or pulmonary hypertension, creatinine clearance less than 60ml/min);

   2. Individual has a confirmed diagnosis of myelodysplastic syndrome with ring sideroblasts (MDS-RS) OR myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) and ALL of the following:

      1. An IPSS-R category of very low, low, or intermediate risk as defined by the Revised International Prognostic Scoring System (IPSS-R). <Risk Assessment Calculator is available at https://ipssrbasic.mds-foundation.org/ >;

      2. Individual has documented hemoglobin <10g/dL;

      3. Individual required ≥2 RBC units in the previous 8 weeks;

      4. ONE of the following:

         1. Documented ring sideroblasts ≥15%; OR

         2. Documented ring sideroblasts ≥5% with an SF3B1 mutation;

      5. Individual has ONE of the following:

         1. An inadequate response to prior treatment with an erythropoiesis stimulating agent (ESA);

         2. FDA-labeled contraindication or hypersensitivity to ALL ESAs; OR

         3. Inability to receive ESA treatment as defined by a serum erythropoietin level >200 U/L;

      6. Individual does not have MDS associated with deletion 5q (del5q) cytogenetic abnormality; AND

      7. Individual has not been treated previously with disease-modifying agents for MDS; OR

   3. The individual has a confirmed diagnosis of myelodysplastic syndrome and ALL of the following:

      1. An IPSS-R category of very low, low, or intermediate risk as defined by the Revised International Prognostic Scoring System (IPSS-R). <Risk Assessment Calculator is available at https://ipssrbasic.mds-foundation.org/ >

      2. Individual has documented hemoglobin <10g/dL;

      3. Individual required ≥2 RBC units in the previous 8 weeks;

      4. Individual is erythropoiesis-stimulating agent (ESA)-naïve (without prior ESA use); AND

      5. Individual has an endogenous serum erythropoietin less than 500 U/mL;

3. If female, provider has confirmed individual is not pregnant prior to treatment and will use an effective method of contraception during treatment and for at least 3 months after treatment;

4. Other causes of anemia (e.g., hemolysis, bleeding, recent major surgery, vitamin deficiency, etc.) have been ruled out;

5. The prescriber is or has consulted with a specialist in an area of the individual's diagnosis (e.g., hematologist or oncologist);

6. The individual does not have any contraindication(s) to therapy with the requested agent; AND

7. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 6 months

Renewal Evaluation

Reblozyl (luspatercept-aamt) will be approved for continued use when ALL of the following criteria are met:

1. Individual has been previously approved for the requested agent through the BCBSMS PA process;

2. Individual has documented clinical improvement (i.e., reduction in transfusion requirements from pretreatment baseline);

3. The individual does not have any contraindication(s) to therapy with the requested agent; AND

4. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

1. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

2. appropriate with regard to standards of good medical practice; and

3. not solely for the convenience of the Member, his or her Provider; and

4. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

POLICY HISTORY

05/01/2020: New policy added.

06/26/2020: Code Reference section updated to add new HCPCS code J0896, effective 07/01/2020.

07/13/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Reblozyl (luspatercept-aamt). Policy section updated to revise initial and renewal evaluation criteria. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and to add information regarding BCBSMS request for medical records. Sources updated. Code Reference section updated to change "Covered Codes" to "Medically Necessary Codes."

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

06/27/2024: Policy updated to extend Length of Approval to 6 months.

06/03/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Reblozyl (luspatercept-aamt). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated regarding those with a confirmed diagnosis of β-thalassemia and myelodysplastic syndrome. Added criteria regarding prescriber requirement, contraindications to therapy, and dose requirements. Renewal criteria updated regarding approval through documented clinical improvement and contraindications to therapy. Sources updated.

SOURCE(S)

1. An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Adults Who Require Regular Red Blood Cell Transfusions Due to Beta (â) Thalassemia (BELIEVE). November 2019.

2. Cappelini MD, Viprakasit V, Taher A, et al. The BELIEVE Trial: results of a phase 3, randomized, double-blind, placebocontrolled study of luspatercept in adult beta-thalassemia patients who require regular red blood cell (RBC) transfusions. Blood. 2018; 132: 163. doi: 10.1182/blood-2018-163.

3. Greenberg P, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System for Myelodysplastic Syndromes. Blood 2012; 120 (12): 2454–2465. doi: https://doi.org/10.1182/blood-2012-03-420489.

4. Piga A, Perrotta S, Gamberini M, et al. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia. Blood. 2019; 133(12): 1279–1289. doi: 10.1182/blood-2018-10-879247.

5. Reblozyl prescribing information. Celgene Corporation. May 2024. Last accessed April 2025.

6. The Myelodysplastic Syndromes Foundation, Inc. Advanced Calculator. https://ipssrbasic.mds-foundation.org/

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

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