Colorado Rocky Mountain HP: Reblozyl Coverage

Coverage Criteria for Reblozyl (luspatercept-aamt)

inv-01: Beta thalassemia – Initial Therapy

Covered when ALL of the following are met for adult patients with beta thalassemia (Initial Therapy):

Beta thalassemia initial therapy: Diagnosis of anemia due to beta thalassemia (including beta+ thalassemia, beta0 thalassemia, and hemoglobin E/beta thalassemia); patient is 18 years of age or older; patient is transfusion dependent as evidenced by both of the following in the previous 24 weeks: has required regular transfusion of at least six units of packed red blood cells (PRBC) AND no transfusion-free period greater than 35 days; prescribed by, or in consultation with, a hematologist or other specialist with expertise in beta thalassemia; dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months.

inv-02: Myelodysplastic Syndromes (MDS) – Initial Therapy

Covered when ALL of the following are met for symptomatic anemia in lower-risk MDS (Initial Therapy):

MDS initial therapy: Diagnosis of symptomatic anemia due to myelodysplastic syndrome (MDS); patient has lower-risk disease defined by IPSS-R as Very Low, Low, or Intermediate; patient does not have a confirmed del(5q) mutation; and one of the following: (a) both ring sideroblasts < 15% (or < 5% with an SF3B1 mutation) AND serum erythropoietin ≤ 500 mU/mL; OR (b) ring sideroblasts ≥ 15% (or ≥ 5% with an SF3B1 mutation); prescribed by, or in consultation with, a hematologist/oncologist or other specialist with expertise in MDS; dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months.

inv-03: MDS/MPN – Initial Therapy

Covered when ALL of the following are met for MDS/MPN:

MDS/MPN initial therapy: Diagnosis of anemia due to myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN); presence of an SF3B1 mutation; thrombocytosis defined as platelet count ≥ 450 x 10^9/L; prescribed by, or in consultation with, a hematologist/oncologist or other specialist with expertise in MDS/MPN; dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months.

inv-04: Myelofibrosis-associated anemia – Initial Therapy

Covered when ALL of the following are met for myelofibrosis-associated anemia (Initial Therapy):

Myelofibrosis-associated anemia initial therapy: Diagnosis of myelofibrosis-associated anemia; and one of the following: (1) ongoing symptomatic splenomegaly and/or constitutional symptoms AND used in combination with Jakafi (ruxolitinib); OR (2) no splenomegaly or constitutional symptoms; OR (3) splenomegaly and constitutional symptoms well controlled on a current JAK inhibitor (examples: fedratinib, ruxolitinib, momelotinib, pacritinib) AND used in combination with a JAK inhibitor; prescribed by, or in consultation with, a hematologist/oncologist or other specialist with expertise in myelofibrosis; dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months.

inv-05: Continuation Therapy / Reauthorization

Continuation of Therapy for covered indications:

Continuation/reauthorization: Documentation of a positive clinical response to Reblozyl (e.g., reduction in transfusion burden, increase in hemoglobin from baseline); prescribed by, or in consultation with, an appropriate specialist; dosing in accordance with FDA-approved labeling; reauthorization for no more than 12 months.

inv-06: FDA and guideline-concordant covered populations

Covered when ONE of the following FDA-indicated or guideline-supported clinical scenarios is met

Covered indications: Adult patients with anemia in beta thalassemia who require regular red blood cell transfusions (FDA indication).

Covered indications: Adult patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (IPSS-R) with anemia without prior ESA use (ESA-naive) who may require regular RBC transfusions (FDA indication).

Covered indications: Adult patients with very low-, low-, or intermediate-risk MDS with ring sideroblasts (MDS-RS) or MDS/MPN-RS-T with anemia failing an ESA and requiring two or more RBC units over 8 weeks (FDA indication).>=2 RBC units per 8 weeks

inv-07: NCCN contextual criteria

NCCN-specified supportive criteria for lower-risk MDS

NCCN recommendations: NCCN recommends Reblozyl for lower-risk MDS with symptomatic anemia without del(5q) and ring sideroblasts ≥ 15% (or ≥ 5% with an SF3B1 mutation). NCCN also recommends Reblozyl (2A) for lower-risk MDS with ring sideroblasts < 15% (or < 5% with SF3B1 mutation) when serum erythropoietin ≤ 500 mU/mL. Lower-risk is defined as IPSS-R Very Low, Low, or Intermediate. NCCN defines lack of response to luspatercept as absence of a ≥1.5 g/dL hemoglobin rise or lack of decreased RBC transfusion requirement by 6 to 8 weeks.

Reblozyl is not proven or medically necessary for the following indications: non-transfusion dependent beta thalassemia, beta thalassemia in pediatric patients, sickle beta thalassemia (hemoglobin S/beta thalassemia), and alpha thalassemia.

Per the FDA-labeled limitation of use, Reblozyl 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 in place of transfusion for urgent hemoglobin correction.

Use of Reblozyl for the listed excluded indications — including non-transfusion dependent beta thalassemia, pediatric beta thalassemia, sickle beta thalassemia (HbS/beta thalassemia), and alpha thalassemia — is considered not proven and not medically necessary and may be denied.

Use of Reblozyl solely to immediately correct anemia instead of providing an RBC transfusion is outside the labeled indication and is considered not medically necessary under the policy limitation of use.

Coding and Key Clinical Thresholds

Applicable HCPCSHCPCS

J0896

Injection, luspatercept-aamt, 0.25 mg.

Applicable ICD-10 Diagnosis CodesICD-10

D46.1	Refractory anemia with ring sideroblasts.
D46.20	Refractory anemia with excess of blasts, unspecified.
D46.21	Refractory anemia with excess of blasts 1.
D46.22	Refractory anemia with excess of blasts 2.
D46.B	Refractory cytopenia with multilineage dysplasia and ring sideroblasts.
D56.1	Beta thalassemia.
D56.5	Hemoglobin E-beta thalassemia.

Product identifiersNDC | mixed

NDC/Codes in package insert

Reblozyl (luspatercept) product coding as per package insert (specific NDCs not listed in provided text)

Transfusion burden — Transfusion-dependent beta thalassemia

Minimum PRBC transfusions (24 weeks)At least six units of packed red blood cells (PRBC) required in the previous 24 weeks

Maximum transfusion-free intervalNo transfusion‑free period greater than 35 days during the prior 24 weeks

Clinical contextUsed to establish transfusion‑dependency for adult patients with beta thalassemia per BELIEVE trial enrollment and policy coverage rationale

Ring sideroblast threshold

Primary ring sideroblast thresholdRing sideroblasts ≥ 15%

Reduced threshold with SF3B1 mutation

Prior Authorization, Documentation, and Limitations

Prior Authorization

Prior Authorization and Duration

Prior authorization is required for initiation of Reblozyl (luspatercept) therapy. Initial authorization will be for no more than 12 months. Reauthorization (continuation) review will require documentation of a positive clinical response (for example, reduction in transfusion burden or increase in hemoglobin from baseline) and, when applicable, ongoing specialist involvement and dosing consistent with FDA labeling. Duration limits: initial and each reauthorization period up to 12 months.

Initial authorization: ≤ 12 months
Reauthorization: ≤ 12 months; requires documented clinical response

Prior Authorization

Prior Authorization Requirement

Prior authorization must confirm the member meets an FDA‑indicated population and the policy clinical criteria. Supported indications include: transfusion‑dependent beta thalassemia in adults; ESA‑naïve very low‑ to intermediate‑risk MDS who may require regular RBC transfusions; and MDS‑RS or MDS/MPN‑RS‑T with anemia failing an ESA and requiring ≥2 RBC units over 8 weeks. Therapy must be prescribed by or in consultation with an appropriate specialist (hematologist, oncologist, or other with relevant expertise).

Clinical Background

Beta-thalassemias are inherited disorders caused by defective synthesis of the beta chains of hemoglobin, producing variable degrees of anemia. Disease severity ranges from minimal anemia to transfusion dependence; patients who are transfusion-dependent face risks of iron overload and related complications. Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis and cytopenias, and risk stratification (e.g., IPSS-R) informs treatment decisions. Luspatercept (Reblozyl) is an erythroid maturation agent that enhances late-stage erythropoiesis and is used in specific adult patient populations as defined by FDA indications and guideline recommendations.

Key Definitions

Transfusion dependent — Definition (beta thalassemia)

Definition (policy)Transfusion dependent: patients requiring regular RBC transfusions as evidenced by transfusion history meeting policy thresholds (e.g., ≥6 units/24 weeks and no transfusion‑free period >35 days)

Clinical significanceDistinguishes patients with beta thalassemia who require ongoing transfusion support and are eligible for therapy per BELIEVE trial criteria

Age contextApplied to adult patients (≥18 years) in policy coverage criteria for beta thalassemia

Lower‑risk MDS (IPSS‑R) — Definition and context

IPSS‑R categories includedLower‑risk MDS defined as IPSS‑R Very Low, Low, or Intermediate

Ring sideroblast/SF3B1 criteriaRing sideroblast and SF3B1 mutation criteria are applied to determine eligibility (see ring sideroblast thresholds and SF3B1 guidance)

Line of Therapy Considerations

inv-31: second-line | first-line (ESA-naive context in COMMANDS compared to epoetin alfa)

ESA-naive vs prior-ESA context: Single top-level distinction: patients may be ESA‑naive (as in COMMANDS where luspatercept was compared to epoetin alfa) or have prior ESA exposure/failure (as in MEDALIST); authorization logic should identify which context applies to the patient based on indication and trial/guideline alignment.

inv-32: first-line | second-line

Line of therapy: Placement depends on indication: for ESA‑naive lower‑risk MDS, luspatercept may be used in an ESA‑naive (first‑line biologic) context per COMMANDS; for MDS‑RS or MDS/MPN‑RS‑T, luspatercept is indicated after ESA failure (second‑line) per MEDALIST and FDA labeling.

Biomarker and Genetic Requirements

SF3B1 mutation — Biomarker context

Biomarker requiredPresence of an SF3B1 mutation is required for MDS/MPN coverage and influences ring sideroblast interpretation

Role in MDS/MPNSF3B1 mutation coupled with thrombocytosis identifies MDS/MPN‑RS‑T patients eligible per policy

DocumentationSF3B1 mutation status should be included in clinical documentation for authorization

SF3B1 — Impact on ring sideroblast criteria

Effect on ring sideroblast thresholdPresence of SF3B1 mutation permits lowering the ring sideroblast percentage requirement to ≥5% (otherwise ≥15%)

NCCN alignmentPolicy applies this adjustment per NCCN Drugs & Biologics Compendium recommendations

Dosing and Administration

Regimen	Indication	Coverage
Luspatercept administered subcutaneously every 3 weeks (as in BELIEVE trial)	Adult patients with beta thalassemia requiring regular red blood cell transfusions (6–20 RBC units per 24 weeks) with no transfusion‑free period greater than 35 days	Covered when policy criteria are met (see beta thalassemia initial therapy)
Dosing per FDA label; continue as long as reduction in transfusion requirement is observed or until unacceptable toxicity	Includes beta+ thalassemia, beta0 thalassemia, and hemoglobin E/beta thalassemia enrolled in BELIEVE	Covered when policy criteria are met

Regimen	Indication / Trial context	Coverage
Luspatercept subcutaneously every 3 weeks starting at 1.0 mg/kg with titration up to 1.75 mg/kg	Lower‑risk MDS (IPSS‑R very low, low, intermediate) with symptomatic anemia, including patients with ring sideroblasts (MEDALIST dosing: 1.0 mg up to 1.75 mg/kg); also used in ESA‑naive MDS per COMMANDS context	Covered when policy criteria are met (see MDS initial therapy)
Dosing per MEDALIST and COMMANDS trials and FDA label with possible titration to 1.75 mg/kg	MEDALIST: patients refractory to or unlikely to respond to ESAs (transfusion dependence); COMMANDS: ESA‑naive patients requiring transfusions	Covered when policy criteria are met (including ring sideroblast/SF3B1 and ESA history as applicable)

Regimen	Source / Trials	Coverage
Luspatercept administered subcutaneously every 3 weeks starting at 1.0 mg/kg with possible titration to 1.75 mg/kg	Per MEDALIST (1.0 mg up to 1.75 mg/kg) and COMMANDS (start 1.0 mg/kg with possible titration to 1.75 mg/kg); reflected in FDA prescribing information	Covered when dosing and indication-specific criteria in policy are met

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Reblozyl (luspatercept-aamt) – Medical Benefit Drug Policy (coverage criteria)