Colorado Rocky Mountain Health Plans Reblozyl Coverage Update

Coverage Criteria for Reblozyl (luspatercept‑aamt)

Initial Therapy — Beta thalassemia

Covered when ALL of the following are met for beta thalassemia

Beta thalassemia initial therapy: Diagnosis of anemia due to beta thalassemia (including beta+ thalassemia, beta0 thalassemia, and hemoglobin E/beta thalassemia); age ≥18 years; transfusion dependent defined as at least six units PRBC in the previous 24 weeks AND no transfusion-free period >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 monthsAt least six units PRBC in prior 24 weeks and no transfusion-free period >35 days

From Coverage Rationale

Continuation of Therapy — Beta thalassemia

Continuation criteria for beta thalassemia

Beta thalassemia continuation: 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 or other specialist with expertise; dosing in accordance with FDA-approved labeling; reauthorization for no more than 12 monthsnone specified

Continuation of Therapy

Initial Therapy — MDS

Covered when ALL of the following are met for MDS (symptomatic anemia, lower-risk)

MDS initial therapy: Diagnosis of symptomatic anemia due to myelodysplastic syndrome (MDS); patient has lower-risk disease per IPSS-R (Very Low, Low, or Intermediate); no confirmed del(5q); 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 monthsring sideroblasts %, serum erythropoietin ≤ 500 mU/mL

From Initial Therapy MDS

Continuation of Therapy — MDS

Continuation criteria for MDS

MDS continuation: 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 other specialist with expertise in MDS; dosing in accordance with FDA-approved labeling; reauthorization for no more than 12 monthsnone specified

Continuation of Therapy

Initial Therapy — MDS/MPN

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 monthsSF3B1 mutation present; platelets ≥ 450 x 10^9/L

From Coverage Rationale

Initial Therapy — Myelofibrosis‑associated anemia

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

Myelofibrosis initial therapy options: Diagnosis of myelofibrosis-associated anemia AND one of the following: (1) ongoing symptomatic splenomegaly and/or constitutional symptoms AND used in combination with ruxolitinib (Jakafi); OR (2) no splenomegaly or constitutional symptoms; OR (3) splenomegaly and constitutional symptoms well controlled on current JAK inhibitor (e.g., 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 monthsnone specified

From Initial Therapy Myelofibrosis

Continuation of Therapy — Myelofibrosis

Continuation criteria for myelofibrosis-associated anemia

Myelofibrosis continuation: 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 other specialist with expertise in myelofibrosis; dosing in accordance with FDA-approved labeling; reauthorization for no more than 12 monthsnone specified

Continuation of Therapy

Covered indications (FDA and trial-aligned)

Covered when ALL of the following are met for each indicated population:

beta-thalassemia indication: Adult patient with beta-thalassemia who require regular red blood cell (RBC) transfusions, consistent with FDA indication

Supported by BELIEVE trial evidence

MDS ESA-refractory or intolerance (MDS-RS): Adult patient with very low-, low-, or intermediate-risk myelodysplastic syndromes with symptomatic anemia and ring sideroblasts (≥15% or ≥5% with SF3B1 mutation) who has anemia failing an erythropoiesis-stimulating agent and requires two or more RBC units over 8 weeks, consistent with FDA indication≥2 RBC units per 8 weeks

Supported by MEDALIST trial

MDS ESA‑naïve: Adult patient with very low- to intermediate-risk MDS with symptomatic anemia who is ESA‑naïve and requires red blood cell transfusions (e.g., 2–6 units per 8 weeks as in COMMANDS trial) and meets clinical criteria consistent with trial entry2–6 PRBC units per 8 weeks

Reblozyl is not proven or medically necessary for the following diagnoses and populations: non‑transfusion dependent beta thalassemia; beta thalassemia in pediatric patients; sickle beta thalassemia (HbS/beta thalassemia); and alpha thalassemia. These uses are listed in the policy exclusions and may be denied if submitted for coverage.

Reblozyl is not indicated as a substitute for red blood cell (RBC) transfusion when immediate correction of anemia is required. Claims using Reblozyl in place of an urgent transfusion are outside the FDA‑labeled use and may be denied.

Use of Reblozyl for indications listed as not proven or medically unnecessary in this policy (for example, non‑transfusion dependent beta thalassemia, pediatric beta thalassemia, sickle beta thalassemia, or alpha thalassemia) is considered not medically necessary and may be denied.

Reblozyl should not be used as an immediate replacement for RBC transfusion in patients who require urgent correction of anemia. The FDA Limitations of Use specify that Reblozyl is not indicated as a substitute for transfusion when immediate correction is needed; such use is outside the labeled indication and may be denied.

Coding: HCPCS, ICD-10, and Product Codes

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.

Drug/ProductNDC

NDC (per package insert)

Reblozyl (luspatercept-aamt) product codes as per package insert

Transfusion requirement — Beta thalassemia

Transfusion thresholdAt least six units of packed red blood cells (PRBC) in the prior 24 weeks

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

Age requirementPatient is 18 years of age or older

Serum erythropoietin — MDS (ring sideroblasts <15% pathway)

Erythropoietin cutoffSerum erythropoietin ≤ 500 mU/mL

ContextRequired when pathway uses ring sideroblasts <15% (or <5% with SF3B1 mutation) per MDS criteria

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Initial authorization period is 6 months.

Prior authorization required to demonstrate patient meets indication‑specific clinical criteria (age ≥18, diagnosis, biomarker or lab values, transfusion history or ESA status as applicable).
Initial authorization period: 6 months; continuation requests must document ongoing benefit or continued need (see required clinical documentation).

Prior Authorization

Prior Authorization Requirement

Prior authorization will be approved only when the FDA‑indicated diagnosis and indication‑specific criteria are met.

For beta thalassemia: documentation of diagnosis (including beta+ , beta0, HbE/beta), age ≥18, and transfusion dependence (see documentation criteria).
For MDS: documentation of symptomatic anemia, IPSS‑R risk (Very Low, Low, Intermediate), ring sideroblast status and serum erythropoietin level or prior ESA status per indication.
For myelofibrosis‑associated anemia: documentation of diagnosis and JAK inhibitor status when required by indication.

Background and Clinical Context

Beta‑thalassemias and myelodysplastic syndromes (MDS) produce anemia primarily through defective erythropoiesis. Reblozyl (luspatercept‑aamt) is an erythroid maturation agent that enhances late‑stage erythropoiesis by binding select TGF‑β superfamily ligands. Clinical trial evidence supporting its FDA indications includes the BELIEVE trial for transfusion‑dependent beta thalassemia and the MEDALIST and COMMANDS trials for MDS, which demonstrated reductions in transfusion burden and increased rates of transfusion independence in specified patient populations.

Definitions and Key Terms

Transfusion-dependent beta thalassemia — definition

DefinitionRequiring regular red blood cell (RBC) transfusion of at least six units PRBC in the prior 24 weeks

Transfusion-free intervalNo transfusion-free period greater than 35 days during that 24‑week period

Trial-aligned rangeBELIEVE trial enrollment included patients receiving 6–20 RBC units per 24 weeks with no transfusion‑free period >35 days

Lower‑risk MDS (IPSS‑R)

IPSS-R categoriesLower‑risk MDS defined as Very Low, Low, or Intermediate per IPSS‑R

Applies toPatients considered for luspatercept for symptomatic anemia

Line of Therapy and Treatment Sequence

first-line | second-line — 1 top-level node

Line of therapy (MDS ESA-exposure context): MEDALIST enrolled patients who were ESA-refractory or unlikely to respond; COMMANDS enrolled ESA‑naïve patients. Coverage includes both ESA‑naïve (first-line for anemia per COMMANDS evidence) and patients who have failed or are unlikely to respond to ESAs (subsequent line per MEDALIST and FDA labeling).

first-line | second-line — 1 top-level node

Line of therapy: Includes ESA‑naïve patients (first-line for anemia in lower-risk MDS per COMMANDS evidence) and patients who have failed or are unlikely to respond to ESAs (subsequent line per MEDALIST evidence and FDA labeling). NCCN recommendations align with these scenarios.

NCCN alignment

Biomarker and Genetic Test Requirements

SF3B1 — biomarker requirement

BiomarkerSF3B1 status required for certain pathways (in MDS/MPN and affects ring sideroblast thresholds)

RolePresence of SF3B1 allows interpretation of lower ring sideroblast percentage thresholds (e.g., ≥5% or <5%)

Testing implicationSF3B1 mutation testing is relevant when ring sideroblast percentage is near threshold cutoffs

SF3B1 mutation — impact on ring sideroblast threshold

Effect on RS thresholdSF3B1 mutation presence may permit lower ring sideroblast percentage threshold (≥5% rather than ≥15% or <5% rather than <15%)

Applicable pathwaysUsed in MDS ring sideroblast pathways and MDS/MPN coverage where SF3B1 is required

Dosing, Administration, and Regimens

Regimen	Dosing / Schedule	Indication	Coverage
Luspatercept (Reblozyl)
Subcutaneous injection once every 3 weeks; dosing per FDA labeling and clinical trials (trial dosing described as 1.0 mg/kg up to 1.75 mg/kg).
Beta thalassemia (transfusion‑dependent) and lower‑risk MDS populations as studied in pivotal trials.
Covered when clinical criteria are met per policy (see indication‑specific criteria).

Regimen	Dosing / Schedule	Trial / Label Context	Coverage
Luspatercept (Reblozyl)
Administered subcutaneously once every 3 weeks starting at 1.0 mg/kg with possible titration up to 1.75 mg/kg.
ESA‑naïve, very low‑ to intermediate‑risk MDS patients (COMMANDS trial; FDA indication for anemia without prior ESA use).
Covered when patient meets FDA/criteria for ESA‑naïve lower‑risk MDS and other policy requirements (specialist prescribing, documentation).

Regimen	Dosing / Schedule	Trial / Label Context	Coverage
Luspatercept (Reblozyl)
1.0 mg/kg with possible escalation up to 1.75 mg/kg, administered subcutaneously every 3 weeks (MEDALIST dosing).
Lower‑risk MDS with ring sideroblasts who have anemia failing an ESA and requiring transfusions (MEDALIST trial population).
Covered when patient meets FDA/clinic criteria for MDS with prior ESA failure and transfusion requirements per policy.

OpenPayer

Reblozyl (Luspatercept‑Aamt) — Medical Benefit Drug Coverage

Coverage Criteria for Reblozyl (luspatercept‑aamt)

Coding: HCPCS, ICD-10, and Product Codes

Provider Actions, Prior Authorization, and Documentation

Background and Clinical Context

Definitions and Key Terms

Line of Therapy and Treatment Sequence

Biomarker and Genetic Test Requirements

Dosing, Administration, and Regimens