Blue Cross Blue Shield - Iowa Reblozyl Coverage

Coverage and Authorization Criteria

Initial Therapy — Anemia with Beta Thalassemia

Authorization of 16 weeks may be granted for treatment of anemia with beta thalassemia in members 18 years of age or older when all of the following criteria are met:

Beta thalassemia initial criteria: Member is >=18 years; symptomatic anemia evidenced by a pretreatment or pretransfusion hemoglobin (Hgb) level <= 11 g/dL; diagnosis of beta thalassemia or hemoglobin E/beta thalassemia confirmed by hemoglobin electrophoresis/HPLC OR molecular genetic testing; member required at least 6 red blood cell (RBC) units transfused in the previous 24 weeks; Reblozyl is prescribed by, or in consultation with, a hematologist or other specialist with expertise in the diagnosis and management of beta thalassemia.Hgb <= 11 g/dL; >=6 RBC units/24 weeks

If an RBC transfusion occurred prior to dosing, use the pretransfusion Hgb for dosing decisions.

Initial Therapy — Anemia of Myelodysplastic Syndrome or MDS/MPN-RS-T

Authorization of 24 weeks may be granted for the treatment of anemia of myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm in members 18 years of age or older when ALL of the following criteria are met:

MDS / MDS/MPN-RS-T initial criteria: Member is >=18 years; symptomatic anemia evidenced by a pretreatment or pretransfusion Hgb level <= 11 g/dL; other causes of anemia (e.g., GI bleeding, hemolysis, renal disease, nutritional deficiency) have been ruled out and/or addressed; the member meets one of the following: receives regular RBC transfusions defined as >= 2 units per 8 weeks OR has very low- to intermediate-risk MDS OR has MDS/MPN-RS-T; Reblozyl is prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of myelodysplastic syndromes.Hgb <= 11 g/dL; >=2 RBC units/8 weeks

Initial Therapy — Myelofibrosis-associated Anemia

Authorization of 12 months may be granted for the treatment of myelofibrosis-associated anemia when ALL of the following criteria are met:

Myelofibrosis-associated anemia initial criteria: Other causes of anemia (e.g., GI bleeding, hemolysis, renal disease, nutritional deficiency) have been ruled out and/or addressed; Reblozyl is prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of myelodysplastic syndromes or myelofibrosis-associated anemia.

Authorization duration 12 months.

Continuation of Therapy

Authorization of 6 months may be granted for continued treatment when ALL of the following criteria are met:

Continuation criteria: Member achieves or maintains a reduction in RBC transfusion burden; member does not experience unacceptable toxicity from Reblozyl; pre-dose Hgb is <= 11 g/dL (if Hgb > 11 g/dL, the prescriber agrees to hold the dose until Hgb <= 11 g/dL); Reblozyl is prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of the treated indication.Hgb <= 11 g/dL

Continuation authorization duration 6 months.

Covered indications

Covered when criteria mirror clinical trial populations and approved indications

Beta thalassemia indication: Adult patient with beta thalassemia who require regular RBC transfusions.Transfusion-dependent as per BELIEVE trial: 6–20 RBC units/24 weeks with no transfusion-free period >35 days

Reblozyl is indicated for anemia in adult patients with beta thalassemia who require regular RBC transfusions and is not a substitute for immediate transfusion.

MDS indication (after ESA failure): Adult patient with very low- to intermediate-risk MDS with ring sideroblasts (or MDS/MPN-RS-T) who have anemia failing an erythropoiesis-stimulating agent and require >=2 RBC units over 8 weeks.>=2 RBC units/8 weeks

Supported by MEDALIST demonstrating increased transfusion independence (>=8 weeks).

MDS indication (ESA-naive): Adult patient with very low- to intermediate-risk MDS who are transfusion-dependent and ESA-naive.

Coverage will not be provided for members with hemoglobin S/B‑thalassemia or alpha‑thalassemia.

Reblozyl (luspatercept‑aamt) is not indicated as a substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia. It should not be used when urgent transfusion is clinically indicated.

Reblozyl (luspatercept‑aamt) is considered not medically necessary for members who do not meet the clinical criteria set forth in this policy.

Billing and Code References

Procedure/Drug HCPCSHCPCS

J0896

Injection, luspatercept‑aamt; 0.25 mg

Pretreatment / Pretransfusion Hemoglobin

Pretreatment / pretransfusion hemoglobin thresholdHgb <= 11 grams per deciliter

Use for dosing if transfusion occurred prior to doseWhen an RBC transfusion occurred prior to dosing, use pretransfusion Hgb for dosing purposes

Continuation dosing conditionPre-dose Hgb must be <= 11 g/dL; if >11 g/dL prescriber agrees to hold dose until <=11 g/dL

Red Blood Cell Transfusion History — Policy vs BELIEVE Trial

Policy transfusion-history requirement (MDS)>= 2 units per 8 weeks (policy requirement for MDS indication)

Policy transfusion-history requirement (beta thalassemia initial criteria)Member required at least 6 RBC units transfused in the previous 24 weeks (policy for beta thalassemia)

Prior Authorization, Documentation, and Billing Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required for initiation of Reblozyl (luspatercept-aamt). Submit documentation including the diagnosis (beta thalassemia or specified MDS/MDS/MPN-RS-T), pretreatment or pretransfusion hemoglobin (Hgb) level, transfusion history, and prior therapies to support medical necessity. Initial authorizations may be granted for specified durations when clinical criteria are met (see policy for duration by indication).

Required documentation: diagnosis, pretreatment/pretransfusion Hgb level, transfusion history, prior therapies (including prior ESA use or failure where applicable), hemoglobin electrophoresis or HPLC and/or molecular genetic testing for beta thalassemia when applicable.

Documentation Required

Documentation Requirements for Authorization

For initial requests, include pretreatment or pretransfusion Hgb. For beta thalassemia requests include hemoglobin electrophoresis or HPLC results or molecular genetic testing results. For MDS indications include documentation of prior ESA therapy and transfusion burden (e.g., ≥2 units/8 weeks) or ESA‑naive status as applicable. For continuation requests, provide current or recent pretransfusion Hgb and evidence of ongoing benefit.

Dosing Regimens and Administration

Regimen	Dosing schedule	Starting dose and uptitration	Indication / trial context	Coverage status
Subcutaneous luspatercept‑aamt	Every 3 weeks (subcutaneous administration)	Starting dose as described in trials (weight‑based mg/kg) with possible uptitration to 1.25 mg/kg	Anemia reduction in transfusion‑dependent beta thalassemia (BELIEVE trial) — patients received luspatercept mg/kg with possible uptitration to 1.25 mg/kg; also used in lower‑risk MDS indications (MEDALIST, COMMANDS)	Covered

Place in Therapy

first-line

First-line: Indication supported for ESA-naive, transfusion-dependent very low- to intermediate-risk MDS patients as studied in the COMMANDS trial (use as first-line for that population).As per COMMANDS trial

second-line

Second-line: Use after failure of an erythropoiesis-stimulating agent (ESA), consistent with MEDALIST trial entry criteria for refractory patients requiring >=2 RBC units over 8 weeks.>=2 RBC units/8 weeks

Key Definitions and Trial Criteria

Definition of Regular RBC Transfusions (with BELIEVE Context)

Policy definition of regular RBC transfusions (context)Regular RBC transfusions referenced in policy reflect trial context of requiring multiple units over defined intervals for transfusion dependence

BELIEVE trial context for 'regular' transfusionsIn BELIEVE, regular transfusions were 6 to 20 RBC units in 24 weeks prior to randomization

Limitation of use noteReblozyl is not indicated as a substitute for RBC transfusions when immediate correction of anemia is required

Transfusion-Dependent Beta Thalassemia — Trial Definition

Trial definition used for transfusion-dependent beta thalassemiaAdults requiring regular transfusions of 6 to 20 RBC units in the 24 weeks prior to randomization

Additional trial constraint

Clinical Background and Indications

Reblozyl (luspatercept‑aamt) is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. The agent is not a substitute for immediate transfusion and is the first therapy specifically indicated for beta thalassemia. The policy aligns coverage with trial populations and approved indications for related anemias, including certain lower‑risk myelodysplastic syndromes and myelofibrosis‑associated anemia, when the specific clinical criteria in this document are met.

Policy Revision History

2025-03-06policy_effectiveLatest

Current effective date for the policy set to March 6, 2025.

2024-10policy_revision

Policy revised (entry listed as October 2024).

2025-01policy_reviewed

OpenPayer

Reblozyl (luspatercept‑aamt) — Coverage Criteria for Anemia