ModifiedUnitedHealthcarePolicy CS2025D0084P

Reblozyl (luspatercept-aamt) — Coverage Criteria for Anemia in Hematologic Disorders

Defines UnitedHealthcare's medical benefit drug policy coverage criteria for Reblozyl (luspatercept-aamt) for adults with transfusion-dependent beta thalassemia, lower‑risk MDS, MDS/MPN overlap, and myelofibrosis‑associated anemia; includes initial and continuation authorization rules, biomarker requirements, dosing expectations, and excluded indications.

Policy Summary

PayerUnitedHealthcare

PolicyReblozyl (luspatercept-aamt) — Coverage Criteria for Anemia in Hematologic Disorders

Policy CodePolicy CS2025D0084P

Change TypeAdded MDS/MPN and myelofibrosis indicationsrevised MDS biomarker criteriaauthorization limits

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization with documentation of diagnosis, required biomarkers (e.g., SF3B1 for MDS/MPN), specialist involvement, and evidence of benefit for reauthorization.

SourceLink

POLICY UPDATE CHANGES

UnitedHealthcare recognizes indications and uses listed in the NCCN Drugs and Biologics Compendium with Categories 1, 2A, and 2B as proven and medically necessary; Category 3 is unproven and not medically necessary.

Removed language indicating Reblozyl was proven and/or medically necessary for the treatment of symptomatic anemia in ESA‑naïve patients with MDS.

Revised MDS coverage criteria to define eligible lower‑risk patients and biomarker‑based pathways (ring sideroblasts and serum erythropoietin ≤ 500 mU/mL).

Added language indicating Reblozyl is proven and medically necessary for anemia in patients with myelodysplastic syndrome/myeloproliferative overlap neoplasm (MDS/MPN).

Added coverage and authorization criteria for myelofibrosis‑associated anemia, including specified scenarios for use with JAK inhibitors.

Defined initial authorization and reauthorization periods (no more than 12 months) and required prescriber specialty and dosing per FDA label for added indications.

Updated Clinical Evidence/Supporting Information and archived previous policy version CS2025D0084O.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

6 unitsminimum PRBC transfusion requirement (24 wks)

35 daysmaximum transfusion‑free period allowed

12 monthsauthorization period (max)

MDS/MPNMDS/MPN added as proven

SF3B1required biomarker for MDS/MPN

Coverage Criteria for Reblozyl (luspatercept-aamt)

Initial Therapy

Reblozyl is proven and medically necessary for the treatment of myelofibrosis-associated anemia who meet all of the following criteria:

ALL of the following

Diagnosis of myelofibrosis-associated anemia
One of the following:
- Option 1
  - Ongoing symptomatic splenomegaly and/or constitutional symptoms
  - Used in combination with Jakafi (ruxolitinib)
- No splenomegaly or constitutional symptoms
- Option 3
  - Splenomegaly and constitutional symptoms well controlled on current JAK inhibitor [e.g., Inrebic (fedratinib), Jakafi (ruxolitinib), Ojjaara (momelotinib), Vonjo (pacritinib)]
  - Used in combination with a JAK inhibitor [e.g., Inrebic (fedratinib), Jakafi (ruxolitinib), Ojjaara (momelotinib), Vonjo (pacritinib)]
Prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of myelofibrosis
Dosing is in accordance with the U.S. FDA approved labeling
Initial authorization will be for no more than 12 months

Continuation of Therapy

Documentation of a positive clinical response to Reblozyl (e.g., reduction in transfusion burden, increase in hemoglobin from baseline)
Reblozyl is prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of myelofibrosis
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months

Coding and Diagnostic Codes

Applicable HCPCSHCPCSCovered

J0896

Injection, luspatercept-aamt, 0.25 mg

Relevant ICD-10-CM 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

Transfusion requirement (beta thalassemia)

Transfusion requirement (numeric)≥ 6 units packed red blood cells (PRBC) in the prior 24 weeks

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

Age requirementPatient age ≥ 18 years for adult transfusion‑dependent indication

PrescriberPrescribed by or in consultation with a hematologist or specialist with expertise in beta thalassemia

Authorization durationInitial authorization limited to no more than 12 months

Serum erythropoietin threshold (MDS eligibility)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Reblozyl (luspatercept-aamt) for all covered indications (beta thalassemia, MDS, MDS/MPN, and myelofibrosis-associated anemia). Initial authorization will be limited to no more than 12 months. Reauthorization (continuation) requests are also limited to no more than 12 months and require documentation of a positive clinical response.

Initial authorization duration: ≤ 12 months
Reauthorization duration: ≤ 12 months (requires documented positive clinical response)

Documentation Required

Required Clinical Documentation

Provide clinical documentation to support the diagnosis and indication (e.g., beta thalassemia, MDS with ring sideroblasts, MDS/MPN with SF3B1 mutation, myelofibrosis-associated anemia), relevant biomarkers (e.g., SF3B1 mutation when required), transfusion history or transfusion-dependence metrics, platelet counts where applicable (e.g., thrombocytosis ≥ 450 x 10^9/L for MDS/MPN), and prior therapies (including ESA use or failure for MDS where referenced).

Covered Regimens and Combination Therapies

Clinical context	Required condition / combination	Examples of JAK inhibitors	Coverage status
Myelofibrosis-associated anemia with ongoing symptomatic splenomegaly and/or constitutional symptoms	Must be used in combination with ruxolitinib (Jakafi) per policy option for this scenario	Jakafi (ruxolitinib)	Covered when criteria met
Myelofibrosis-associated anemia with splenomegaly and constitutional symptoms well controlled on current JAK inhibitor	Used in combination with a JAK inhibitor while symptoms remain controlled	Inrebic (fedratinib); Jakafi (ruxolitinib); Ojjaara (momelotinib); Vonjo (pacritinib)	Covered when criteria met
Myelofibrosis-associated anemia without splenomegaly or constitutional symptoms	May be used as monotherapy (no concomitant JAK inhibitor required per policy option)	—	Covered when criteria met

Covered clinical context	Therapy allowed	Prescriber / Dosing requirement	Coverage status
Myelofibrosis-associated anemia with ongoing symptomatic splenomegaly and/or constitutional symptoms	Reblozyl in combination with a JAK inhibitor (ruxolitinib) as specified	Prescribed by or in consultation with a hematologist/oncologist or specialist; dosing per U.S. FDA labeling	Covered when criteria met
Myelofibrosis-associated anemia with no splenomegaly or constitutional symptoms	Reblozyl monotherapy permitted per policy	Prescribed by or in consultation with a hematologist/oncologist or specialist; dosing per U.S. FDA labeling	Covered when criteria met
Myelofibrosis-associated anemia with splenomegaly and symptoms well controlled on current JAK inhibitor	Reblozyl may be used in combination with the current JAK inhibitor	Prescribed by or in consultation with a hematologist/oncologist or specialist; dosing per U.S. FDA labeling	Covered when criteria met

JAK inhibitor	Scenario / example use	Notes	Coverage status
Ruxolitinib (Jakafi)	Use with Reblozyl when ongoing symptomatic splenomegaly and/or constitutional symptoms are present	Explicitly listed in policy as the JAK inhibitor paired with Reblozyl for symptomatic splenomegaly scenarios	Covered when criteria met
Fedratinib (Inrebic)	Example of a current JAK inhibitor when splenomegaly and symptoms are well controlled on therapy; Reblozyl may be continued in combination	Listed as an example JAK inhibitor in policy language	Covered when criteria met
Momelotinib (Ojjaara)	Example of a current JAK inhibitor used when symptoms are well controlled; combination with Reblozyl permitted	Listed among example JAK inhibitors in policy text	Covered when criteria met
Pacritinib (Vonjo)	Example of a current JAK inhibitor used when symptoms are well controlled; combination with Reblozyl permitted	Listed among example JAK inhibitors in policy text	Covered when criteria met

Definitions and Key Terms

Transfusion‑dependent beta thalassemia — definition

Transfusion‑dependent definition (PRBC units)≥ 6 units PRBC in 24 weeks

Maximum transfusion‑free intervalNo transfusion‑free period > 35 days in the prior 24 weeks

Clinical noteUsed to establish eligibility for Reblozyl initial therapy in adult beta thalassemia

Lower‑risk MDS (eligible)

IPSS‑R risk requirementIPSS‑R category: Very Low, Low, or Intermediate

del(5q) exclusionPatient must not have a confirmed del(5q) mutation

Indication

Biomarker and Laboratory Requirements

SF3B1 — biomarker requirement

BiomarkerSF3B1 mutation required for MDS/MPN with anemia indication

FunctionDetermines eligibility and modifies ring sideroblast thresholds where applicable

Documentation needInclude molecular testing result in prior authorization record

Ring sideroblasts — thresholds and alternative paths

Ring sideroblast thresholdsEither: < 15% (or <5% with SF3B1 mutation) OR ≥ 15% (or ≥5% with SF3B1 mutation) — either path can satisfy MDS eligibility

Context of useDetermines eligibility for lower‑risk MDS initial therapy for Reblozyl

Line of Therapy Statements

first-line | second-line

MDS prior therapy context: MEDALIST included patients refractory to or unlikely to respond to ESAs; COMMANDS compared luspatercept to epoetin alfa in ESA‑naive patients — policy references ESA responsiveness when determining eligibility for MDS indications.

first-line

Initial therapy: Use as initial therapy when criteria met (see Initial Therapy nodes).

Initial authorization up to 12 months.

not_specified

Not specified: Line of therapy not specified in policy for this clinical context; follow criteria-based eligibility.

Background and Clinical Context

Luspatercept is a recombinant fusion protein that binds selected transforming growth factor‑β (TGF‑β) superfamily ligands and enhances late‑stage erythropoiesis. Clinically, it is used to address ineffective erythropoiesis in disorders such as transfusion‑dependent beta thalassemia and certain myelodysplastic syndromes; transfusion‑dependent beta thalassemia is characterized by defective beta‑globin synthesis and may require regular RBC transfusions, with attendant risk of iron overload.

Policy Summary

PayerUnitedHealthcare

PolicyReblozyl (luspatercept-aamt) — Coverage Criteria for Anemia in Hematologic Disorders

Policy CodePolicy CS2025D0084P

Change TypeAdded MDS/MPN and myelofibrosis indicationsrevised MDS biomarker criteriaauthorization limits

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization with documentation of diagnosis, required biomarkers (e.g., SF3B1 for MDS/MPN), specialist involvement, and evidence of benefit for reauthorization.

SourceLink

On This Page

Serum erythropoietin (EPO) thresholdEPO ≤ 500 mU/mL

ContextRequired when ring sideroblasts <15% (or <5% with SF3B1 mutation) as part of lower‑risk MDS eligibility

Reference sourceNCCN‑aligned criteria and policy initial therapy language

Ring sideroblasts — alternative paths and thresholds

Alternative path ARing sideroblasts < 15% (or <5% with SF3B1 mutation) AND serum erythropoietin ≤ 500 mU/mL

Alternative path BRing sideroblasts ≥ 15% (or ≥5% with SF3B1 mutation)

UseEither path A or B satisfies ring sideroblasts‑based eligibility for lower‑risk MDS initial therapy

Thrombocytosis for MDS/MPN

Thrombocytosis numeric thresholdPlatelet count ≥ 450 × 10^9/L

IndicationRequired for MDS/MPN initial therapy eligibility

DocumentationPlatelet count must be documented in clinical record for authorization

Serum erythropoietin — policy reference

Reiterated EPO thresholdSerum erythropoietin ≤ 500 mU/mL used in MDS initial therapy criteria

Applied whenRing sideroblasts <15% (or <5% with SF3B1 mutation)

PurposeTo identify patients unlikely to respond to ESAs and eligible for luspatercept per policy

Platelet count for thrombocytosis

Numeric platelet thresholdPlatelet count ≥ 450 × 10^9/L used to define thrombocytosis in MDS/MPN criteria

RolePart of required criteria for MDS/MPN initial therapy along with SF3B1 mutation

Authorization notePlatelet value should be included in prior authorization documentation

Document diagnosis and supporting labs/biomarkers (e.g., SF3B1 mutation, ring sideroblast percentage, serum erythropoietin)
Transfusion history: units and frequency (e.g., ≥6 PRBC in 24 weeks and no transfusion-free period >35 days for beta thalassemia)
Prior ESA therapy status for MDS: refractory to, unlikely to respond to, or intolerant of ESAs

Documentation Required

Reauthorization: Evidence of Clinical Response

Reauthorization requests must include evidence of a positive clinical response to Reblozyl, such as a reduction in transfusion burden or an increase in hemoglobin from baseline. Lack of adequate documentation of response may lead to denial of continued therapy.

Examples of acceptable response documentation: decrease in number of PRBC units transfused over a comparable time period; hemoglobin rise from baseline sustained on therapy

Documentation Required

Prescriber Qualification

Prescriptions must be issued by, or in consultation with, a hematologist, oncologist, or other specialist with relevant expertise in the diagnosis and management of the specified disorder (beta thalassemia, MDS/MDS‑MPN, or myelofibrosis). Consult notes must be included when applicable.

Prescriber requirement: hematologist/oncologist or specialist with relevant expertise
If prescribed by another clinician, include formal consultation or co-management documentation

Billing Rule

FDA‑Approved Dosing and Quantity/Duration Limits

Dosing must follow the U.S. FDA‑approved labeling. Requests that propose dosing regimens inconsistent with FDA‑approved dosing or that exceed approved dose or frequency may be denied. Requests for quantities or durations that exceed the stated reauthorization limits (≤ 12 months) require prior approval and justification.

Dosing must be per FDA labeling (initial and titration limits)
Deviation from FDA dosing or requests exceeding the stated reauthorization period may be denied

Note

Therapy Context and Combination with JAK Inhibitors

Therapy context and combination use: For myelofibrosis‑associated anemia, Reblozyl may be covered when used in the specified clinical scenarios (e.g., ongoing symptomatic splenomegaly and/or constitutional symptoms used in combination with Jakafi/ruxolitinib, or splenomegaly and symptoms well controlled on a current JAK inhibitor). Include documentation of concurrent JAK inhibitor therapy when applicable and rationale for combination use.

If used with a JAK inhibitor, document the specific agent and clinical rationale (e.g., ruxolitinib)
Document symptom and splenomegaly status per policy criteria

Denial Risk

Denial Triggers / Risk Areas

Denial triggers — common reasons for denial include failure to document the required diagnosis or indication, lack of required biomarker results (e.g., SF3B1 mutation when indicated), failure to meet platelet threshold for MDS/MPN, absence of specialist prescriber or consultation, dosing inconsistent with FDA labeling, and inadequate documentation of clinical response for reauthorization.

Missing diagnosis or insufficient clinical evidence
No required biomarker (e.g., SF3B1) when indicated
Prescriber not a specialist and no consultation on file
Dosing not in accordance with FDA labeling
Insufficient documentation of response at reauthorization

Applies to lower‑risk MDS initial therapy eligibility for Reblozyl

Lower risk MDS — IPSS‑R categories

IPSS‑R categoriesVery Low, Low, or Intermediate

ContextDefines 'lower risk' for Reblozyl eligibility in MDS per policy and NCCN reference

ApplicationRequired for initial therapy consideration

Lack of response to luspatercept (per NCCN)

NCCN definition of nonresponseLack of 1.5 g/dL rise in hemoglobin or lack of a decrease in RBC transfusion requirement by 6 to 8 weeks of treatment

Use in policyDefines lack of response to luspatercept for clinical decision‑making and reauthorization contexts

TimeframeAssessed at 6–8 weeks of treatment per NCCN language

Reblozyl (luspatercept‑aamt) — policy statement

Policy statementReblozyl (luspatercept‑aamt) is proven and medically necessary for anemia in MDS/MPN when criteria are met

DosingDosing must be in accordance with the U.S. FDA approved labeling

AuthorizationInitial authorization up to 12 months; reauthorization limited to no more than 12 months

Thrombocytosis — platelet threshold

Thrombocytosis thresholdPlatelet count ≥ 450 × 10^9/L

ContextSpecified for MDS/MPN initial therapy eligibility

DocumentationPlatelet count must be documented for authorization

SF3B1 mutation — requirement

Required molecular markerPresence of an SF3B1 mutation is required for MDS/MPN indication

RoleUsed both to establish MDS/MPN eligibility and to interpret ring sideroblast thresholds

DocumentationSF3B1 mutation status must be included in clinical documentation for authorization

Specialist — required prescriber expertise

Prescriber qualificationPrescribed by, or in consultation with, a hematologist, oncologist, or other specialist with relevant expertise

Applies toAll indications in policy (MDS, MDS/MPN, myelofibrosis, beta thalassemia) where specified

DocumentationSpecialist involvement must be documented in authorization request

DocumentationBone marrow/pathology report showing ring sideroblast percentage required

Serum erythropoietin — reiterated requirement

Serum erythropoietin (EPO) thresholdEPO ≤ 500 mU/mL reiterated as a requirement when ring sideroblasts are <15% (or <5% with SF3B1)

Clinical roleUsed to identify patients unlikely to respond to ESAs and eligible for Reblozyl

SourcePolicy initial therapy language and revision notes

SF3B1 — reiterated biomarker requirement

SF3B1 requirement reiteratedSF3B1 mutation must be present for MDS/MPN indication per policy language

Interplay with ring sideroblastsSF3B1 presence changes ring sideroblast percentage thresholds used in MDS criteria

Authorization implicationMolecular testing must be provided for prior authorization of MDS/MPN cases