UnitedHealthcare Reblozyl Coverage Update

Coverage and Medical Necessity Criteria

Initial Therapy — Beta thalassemia

Covered when ALL of the following are met for adult transfusion-dependent beta thalassemia:

Beta thalassemia initial therapy: Diagnosis of anemia due to beta thalassemia (including beta+ thalassemia, beta0 thalassemia, and hemoglobin E/beta thalassemia)

Age: Patient is 18 years of age or older

Transfusion dependence: Patient is transfusion dependent as evidenced by BOTH: (1) required >= 6 units PRBC in the previous 24 weeks; AND (2) no transfusion-free period > 35 days

Specialist involvement: Prescribed by, or in consultation with, a hematologist or other specialist with expertise in the diagnosis and management of beta thalassemia

Dosing is in accordance with FDA approved labeling

Authorization duration: Initial authorization will be for no more than 12 months

Continuation Therapy — Beta thalassemia

Continuation criteria for beta thalassemia:

Clinical response: Documentation of a positive clinical response to Reblozyl (e.g., reduction in transfusion burden, increase in hemoglobin from baseline)

Specialist involvement: Prescribed by, or in consultation with, a hematologist or other specialist with expertise in the diagnosis and management of beta thalassemia

Dosing is in accordance with FDA approved labeling

Reauthorization duration: Reauthorization will be for no more than 12 months

Initial Therapy — Lower‑risk MDS

Covered when ALL of the following are met for symptomatic anemia in lower‑risk MDS:

Diagnosis: Symptomatic anemia due to myelodysplastic syndrome (MDS)

Risk category: Patient has lower risk disease as defined by IPSS-R: Very Low, Low, or Intermediate

5q deletion exclusion: Patient does not have a confirmed deletion 5q (del(5q))

Ring sideroblasts/erythropoietin criteria: Either: (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)

Initial Therapy — MDS/MPN overlap

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

Diagnosis: Anemia due to myelodysplastic syndrome/myeloproliferative overlap neoplasm (MDS/MPN)

Biomarker: Presence of an SF3B1 mutation

Thrombocytosis defined as platelet count ≥ 450 x 10^9/L

Specialist involvement and dosing: Prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in MDS/MPN; dosing per FDA approved labeling; initial authorization will be for no more than 12 months

Initial Therapy — Myelofibrosis-associated anemia

Covered when ALL of the following are met for myelofibrosis-associated anemia:

Diagnosis of myelofibrosis-associated anemia

Symptom/context: Either: (A) Symptomatic splenomegaly and/or constitutional symptoms AND used in combination with a JAK inhibitor (examples: fedratinib, ruxolitinib, momelotinib, pacritinib) OR (B) No splenomegaly or constitutional symptoms

Specialist involvement: Prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of myelofibrosis

Dosing and authorization: Dosing is in accordance with FDA approved labeling; initial authorization will be for no more than 12 months

Continuation Therapy — MDS / MDS/MPN / Myelofibrosis

Continuation criteria across MDS, MDS/MPN, and myelofibrosis indications:

Clinical response: Documentation of a positive clinical response to Reblozyl (e.g., reduction in transfusion burden, increase in hemoglobin from baseline)

Specialist involvement: Prescribed by, or in consultation with, an appropriate hematologist/oncologist or other specialist with relevant expertise

Dosing and reauthorization: Dosing is in accordance with FDA approved labeling; reauthorization will be for no more than 12 months

Initial Therapy — Lower-risk MDS (alternate/revised entry)

Covered when ALL of the following are met

Lower-risk MDS initial therapy criteria: Diagnosis of symptomatic anemia due to myelodysplastic syndrome (MDS); lower risk disease per IPSS-R (Very Low, Low, Intermediate); no confirmed del(5q); either (A) ring sideroblasts ≥ 15% (or ≥ 5% with SF3B1 mutation) OR (B) ring sideroblasts < 15% (or < 5% with SF3B1 mutation) AND serum erythropoietin ≤ 500 mU/mL; prescribed by, or in consultation with, a hematologist/oncologist or specialist; dosing per FDA approved labeling; initial authorization ≤ 12 months;

NCCN recommendations referenced; lack of response defined as <1.5 g/dL hemoglobin rise or no decrease in transfusion requirement by 6-8 weeks.

Continuation Therapy — Lower-risk MDS

Covered for reauthorization when ALL of the following are met

Lower-risk MDS continuation therapy criteria: 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, a hematologist/oncologist or specialist; dosing per FDA approved labeling; reauthorization ≤ 12 months;

Initial Therapy — MDS/MPN-RS-T

Covered when ALL of the following are met

MDS/MPN-RS-T initial therapy criteria: Diagnosis of anemia due to MDS/MPN overlap neoplasm (MDS/MPN); presence of SF3B1 mutation; thrombocytosis with platelet count ≥ 450 x 10^9 /L; prescribed by, or in consultation with, a hematologist/oncologist or specialist; dosing per FDA approved labeling; initial authorization ≤ 12 months;

Continuation Therapy — MDS/MPN-RS-T

Covered for reauthorization when ALL of the following are met

MDS/MPN-RS-T continuation therapy criteria: Documentation of a positive clinical response to Reblozyl; prescribed by, or in consultation with, a hematologist/oncologist or specialist; dosing per FDA approved labeling; reauthorization ≤ 12 months;

Initial Therapy — Myelofibrosis-associated anemia (revised)

Covered when ALL of the following are met

Myelofibrosis-associated anemia initial therapy criteria: Diagnosis of myelofibrosis-associated anemia; either (A) symptomatic splenomegaly and/or constitutional symptoms and used in combination with a JAK inhibitor (examples: fedratinib, ruxolitinib, momelotinib, pacritinib) OR (B) no splenomegaly or constitutional symptoms; prescribed by, or in consultation with, a hematologist/oncologist or specialist; dosing per FDA approved labeling; initial authorization ≤ 12 months;

JAK inhibitor examples: Inrebic (fedratinib), Jakafi (ruxolitinib), Ojjaara (momelotinib), Vonjo (pacritinib).

Continuation Therapy — Myelofibrosis-associated anemia

Covered for reauthorization when ALL of the following are met

Myelofibrosis continuation criteria: 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, a hematologist/oncologist or specialist; dosing per FDA approved labeling; reauthorization ≤ 12 months;

Beta thalassemia — Initial and Continuation (revised)

Revised coverage criteria summary

Beta thalassemia criteria (revised): Diagnosis of anemia due to beta thalassemia (including beta+ thalassemia, beta0 thalassemia, hemoglobin E/beta thalassemia); continuation requires documentation of positive clinical response; dosing per FDA approved labeling; other prior criteria revised/removed per policy history.

Specific numeric transfusion-response thresholds previously required were modified per revision.

The policy explicitly lists conditions for which Reblozyl is not proven or medically necessary. These exclusions include non‑transfusion dependent beta thalassemia, beta thalassemia in pediatric patients, sickle beta thalassemia (HbS/beta thalassemia), and alpha thalassemia. Providers should not expect coverage for these indications unless separate contractual or state-specific benefit language overrides the policy.

Per the FDA labeling and reiterated in the policy, Reblozyl is not indicated as a substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia. Orders or requests intended to replace urgent transfusion support should be denied or redirected to appropriate acute transfusion management because Reblozyl does not provide immediate hemoglobin correction.

The policy states that use of Reblozyl for the listed excluded conditions is explicitly not proven or not medically necessary. This means claims for these specific diagnoses are considered unsupported by evidence within the policy and are subject to denial absent compelling, plan‑specific documentation or coverage exceptions.

UnitedHealthcare’s policy clarifies its stance on compendium guidance: indications listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence and Consensus of 1, 2A, and 2B are considered proven and medically necessary, while NCCN Category 3 indications are considered unproven and not medically necessary. Coverage determinations will follow this framework when NCCN compendium listings are relevant to an individual request.

Applicable Codes and Key Numeric Thresholds

Applicable HCPCSHCPCS

J0896

Injection, luspatercept-aamt, 0.25 mg

Applicable ICD-10 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

inv-20: Transfusion units in prior 24 weeks — >= 6 units (key threshold)

Threshold>= 6 units packed red blood cells (PRBC) in the previous 24 weeks

ContextRequired as part of transfusion-dependent beta thalassemia initial therapy criteria

DocumentationTransfusion history must document number of PRBC units over the prior 24 weeks

inv-21: Maximum transfusion-free period — <= 35 days (key threshold)

ThresholdNo transfusion‑free period greater than 35 days (i.e., maximum transfusion‑free interval ≤ 35 days)

Context

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Reblozyl. Initial authorizations will be approved for no more than 12 months. Reauthorizations will also be approved for no more than 12 months and require documentation of a positive clinical response (for example, reduction in transfusion burden or increase in hemoglobin from baseline).

Prior authorization required
Initial authorization ≤ 12 months
Reauthorization ≤ 12 months, requires documented positive clinical response (e.g., reduced transfusion burden or hemoglobin increase)

Documentation Required

Specialist Involvement and FDA‑Concordant Dosing

Prescriptions must be written by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of the relevant condition (e.g., beta thalassemia, MDS, MDS/MPN, myelofibrosis). Dosing must follow the U.S. FDA–approved labeling.

Key Definitions and Eligibility Terms

inv-36: Transfusion dependent (beta thalassemia) — Required regular transfusion of at least six units of PRBC in previous 24 weeks and no transfusion-free period > 35 days.

DefinitionTransfusion dependent = required ≥ 6 units PRBC in previous 24 weeks AND no transfusion‑free period > 35 days

IndicationApplies to adult patients with beta thalassemia for eligibility for Reblozyl

AuthorizationInitial authorization limited to ≤ 12 months; continuation requires documented positive clinical response

inv-37: Lower-risk MDS (policy) — Defined by IPSS-R categories: Very Low, Low, or Intermediate.

DefinitionLower‑risk MDS = IPSS‑R categories Very Low, Low, or Intermediate

Context

Therapy Line Designation

first-line | second-line

Line of therapy grouping: Line of therapy designation references trial populations: MEDALIST (patients refractory to or unlikely to respond to ESAs) and COMMANDS (ESA-naïve patients); use may be first- or second-line depending on prior ESA exposure and guideline context.

second-line

Second-line (COMMANDS population): Designation as second-line corresponds to trial-defined ESA-naïve populations in COMMANDS and settings where luspatercept is used after ESA assessment per guidelines; specific patient-level determination should reference prior ESA exposure and eligibility criteria.

Genomic and Laboratory Biomarker Requirements

inv-42: SF3B1 — Used to interpret ring sideroblasts criteria (<5% or >=5% with SF3B1)

RoleSF3B1 mutation used to interpret ring sideroblast percentage criteria (adjusts cutoffs to <5% or ≥5%)

ApplicationsRequired for MDS ring sideroblasts pathway and for MDS/MPN overlap eligibility

DocumentationLaboratory/genetic testing results should document SF3B1 mutation status

inv-43: SF3B1 — (reinforced entry)

ReinforcementSF3B1 status is explicitly referenced multiple times to adjust ring sideroblast thresholds for MDS indications

ScopeApplies to lower‑risk MDS with ring sideroblasts and MDS/MPN‑RS‑T indications

Permitted Drug Regimens and Dosing Context

Regimen	Indication / Context	Coverage Label
Reblozyl (luspatercept) used in combination with a JAK inhibitor (examples: fedratinib, ruxolitinib, momelotinib, pacritinib)
Myelofibrosis-associated anemia when symptomatic splenomegaly and/or constitutional symptoms are present; used in combination with a JAK inhibitor
Prescribed by or in consultation with a hematologist/oncologist; dosing per FDA labeling; initial authorization ≤ 12 months; continuation requires documentation of positive clinical response

Regimen	Indication / Context	Coverage Label
Reblozyl (luspatercept) per FDA labeling (subcutaneous dosing as indicated)
Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions (transfusion‑dependent)
Prescribed by or in consultation with a hematologist or specialist; dosing according to FDA approved labeling; initial authorization ≤ 12 months; documentation of transfusion dependence (e.g., ≥6 units PRBC in prior 24 weeks and no transfusion‑free period >35 days)

Regimen	Indication / Eligibility	Coverage Label
Reblozyl (luspatercept) per FDA labeling (subcutaneous dosing as indicated)
Anemia in adult patients with very low- to intermediate-risk MDS (IPSS‑R) who are ESA‑naïve and may require regular RBC transfusions; eligibility requires absence of del(5q) and either: (A) ring sideroblasts ≥ 15% (or ≥5% with SF3B1 mutation) OR (B) ring sideroblasts <15% (or <5% with SF3B1 mutation) AND serum erythropoietin ≤ 500 mU/mL
Prescribed by or in consultation with a hematologist/oncologist; dosing per FDA labeling; initial authorization ≤ 12 months; continuation/reauthorization requires documentation of positive clinical response (e.g., reduction in transfusion burden or increase in hemoglobin)

Background and Clinical Rationale

Luspatercept is a recombinant fusion protein that binds select transforming growth factor‑β superfamily ligands and promotes late‑stage erythroid maturation. By enhancing erythropoiesis at the maturation phase, it is used to reduce transfusion burden or increase hemoglobin in specific adult hematologic disorders rather than to provide immediate correction of anemia through transfusion.

Policy Updates and Revision History

11/01/2025policy_revisionLatest

UnitedHealthcare added recognition of indications and uses listed in the NCCN Drugs and Biologics Compendium (Categories 1, 2A, 2B as proven/medically necessary; Category 3 as unproven/not medically necessary).

11/01/2025policy_revision

Removed language indicating Reblozyl is proven and/or medically necessary for ESA‑naïve patients with MDS (language about ESA‑naïve MDS was deleted).

Date not specified in chunk 25/26/27criteria_revision

OpenPayer

Reblozyl (Luspatercept-Aamt) (for Ohio Only)

Coverage and Medical Necessity Criteria

Applicable Codes and Key Numeric Thresholds

Prior Authorization, Documentation, and Provider Requirements

Key Definitions and Eligibility Terms

Therapy Line Designation

Genomic and Laboratory Biomarker Requirements

Permitted Drug Regimens and Dosing Context

Background and Clinical Rationale

Policy Updates and Revision History