Restricted Product(s):

• luspatercept-aamt (Reblozyl^®) subcutaneous injection for administration by a healthcare professional

FDA Approved Use:

• For treatment of anemia in adults with beta thalassemia who require regular red blood cell (RBC) transfusions
• For treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more RBC units over 8 weeks in adults 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)
• 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 red blood cell (RBC) transfusions
• Limitations of use: Not for use as a substitute for RBC transfusions in patients requiring immediate correction of anemia

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

1. The patient is 18 years of age or older; AND
2. The patient has a confirmed diagnosis of beta thalassemia (including Hemoglobin E/beta thalassemia and beta thalassemia with mutation and/or multiplication of alpha globin) [medical record documentation required]; AND
   1. The patient requires regular red blood cell (RBC) transfusions defined as [medical record documentation required]:
      1. At least 6 RBC units within the 24 weeks prior to initiation of treatment with the requested agent; AND
      2. No transfusion-free period ≥35 days during that time; AND
   2. The requested agent is prescribed by or in consultation with a hematologist or specialist in treating beta thalassemia; AND
   3. The patient does not have a diagnosis of Hemoglobin (sickle) S/beta thalassemia or alpha thalassemia (e.g., Hemoglobin H); AND
   4. The patient does not have major organ damage (e.g., liver disease, heart disease, lung disease, or renal insufficiency); OR
3. The patient has a diagnosis of symptomatic anemia associated with a myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm in patients failing an erythropoiesis stimulating agent; AND
   1. The patient has myelodysplastic syndrome with ring sideroblasts (MDS-RS); OR
   2. Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T); AND
   3. The patient has very low- to intermediate-risk disease based on prognostic risk stratification [medical record documentation required]; AND
   4. The patient has ring sideroblasts ≥ 15% [medical record documentation required]; OR
   5. The patient has ring sideroblasts ≥ 5% with an SF3B1 genetic mutation [medical record documentation required]; AND
   6. The patient requires regular red blood cell (RBC) transfusions (defined as at least 2 RBC units within the 8 weeks prior to initiation of treatment with the requested agent) [medical record documentation required]; AND
   7. The patient has one of the following:
      1. The patient has tried and had an inadequate response to prior treatment with an erythropoiesis stimulating agent (ESA) [medical record documentation required]; OR
      2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ESAs [medical record documentation required]; OR
      3. The patient is unable to receive ESA treatment as defined by a serum erythropoietin level > 200 U/L [medical record documentation required]; AND
   8. The requested agent is prescribed by or in consultation with a hematologist, oncologist, or other specialist in treating myelodysplastic syndromes; AND
4. The patient has a diagnosis of myelodysplastic syndromes (MDS) associated anemia, in patients who are ESA-naïve; AND
   1. The patient has very low- to intermediate-risk disease based on prognostic risk stratification [medical record documentation required]; AND
   2. The patient has < 5% blasts in bone marrow [medical record documentation required]; AND
   3. The patient requires regular red blood cell (RBC) transfusions (defined as at least 2 RBC units within the 8 weeks prior to initiation of treatment with the requested agent) [medical record documentation required]; AND
   4. The patient must NOT have had previous erythropoiesis stimulating agent use [medical record documentation required]; AND
   5. The patient has endogenous serum erythropoietin (sEPO) level of < 500 U/L [medical record documentation required]; AND
   6. The patient has baseline hemoglobin levels documented [medical record documentation required]; AND
   7. The requested agent is prescribed by or in consultation with a hematologist, oncologist, or other specialist in treating myelodysplastic syndromes; AND
5. The requested agent will NOT be used as a substitute for RBC transfusions for patients who require immediate correction of anemia; AND
6. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
7. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 180 days (6 months)

Continuation Criteria for Approval:

1. The patient was approved through Blue Cross NC initial criteria for approval; OR
2. The patient would have met initial criteria for approval at the time they started therapy [medical record documentation required]; AND
3. The patient has demonstrated a reduction in RBC transfusion burden following luspatercept treatment [medical record documentation required]; AND
4. IF requesting for myelodysplastic syndromes (MDS) associated anemia in patients who are ESA-naïve, the patient has demonstrated a mean hemoglobin increase ≥ 1.5 g/dL [medical record documentation required]; AND
5. The requested agent is prescribed by or in consultation with a hematologist, oncologist, or other specialist in treating the patient’s diagnosis; AND
6. The requested agent will NOT be used as a substitute for RBC transfusions for patients who require immediate correction of anemia; AND
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
8. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care
   Criteria applies (outlined below) *

Duration of Approval: 365 days (1 year)

*Maximum units allowed for duration of approval

*Site of Care Medical Necessity Criteria

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met:
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR
   4. Re-initiation of therapy, defined as ONE of the following:
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR
   5. Requirement of a change in the requested restricted product formulation; AND
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

References:

All information referenced is from FDA package insert unless otherwise noted below.

1. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. MEDALIST Study. N Engl J Med. 2020;382:140-151.
2. Rund D, Rachmilewitz E. β-Thalassemia. N Engl J Med. 2005;353:1135-46.

Policy Implementation/Update Information:

March 2024: Criteria change: Added indication for the treatment of anemia in adult ESA-naïve patients with very low- to intermediate-risk

MDS who may require regular RBC transfusions per update to FDA label with corresponding criteria and added associated dosing table updates.

October 2021: Criteria change: Added Site of Care medical necessity criteria. Policy notification given 8/2/2021 for effective date 10/1/2021.

June 2021: Criteria change: Updated dosing in FDA Label Reference table. References added.

June 2021: Criteria change: Added specialist requirement and no use as substitution for RBC transfusions to continuation criteria; maximum units; medical policy formatting change. Policy notification given 4/16/2021 for effective date 6/16/2021.

*Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.