State and School Employees' Health Insurance Plan - Reblozyl (luspatercept-aamt)

POLICY NUMBER

S.5.01.552

Reblozyl (luspatercept-aamt)

Please perform a search of the State Health Plan Medical Drug Formulary for drugs administered and billed through the medical setting.

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 individuals 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

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. The individual is ≥18 years of age;

2. ONE of the following:

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

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

         1. The 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. The 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 determined by the Revised International Prognostic Scoring System (IPSS-R). <Risk Assessment Calculator is available at https://ipssrbasic.mds-foundation.org/ >;

      2. The individual has documented hemoglobin <10g/dL;

      3. The 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. The 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. The individual does not have MDS associated with deletion 5q (del5q) cytogenetic abnormality; AND

      7. The 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 the 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. The individual has been previously approved for the requested agent through the BCBSMS review 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

Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

Medical Policy Manual coverage guidelines should not be used in lieu of the Participant's specific benefit plan language outlined in the Mississippi's State and School Employees’ Life and Health Insurance Plan.

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 Participant'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:

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

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

C. not solely for the convenience of the Participant, his or her Provider; and

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

07/01/2023: New policy added.

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 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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