Luspatercept

Luspatercept-aamt is a recombinant fusion protein that binds several endogenous TGF-β superfamily ligands, thereby diminishing Smad2/3 signaling. In models of β-thalassemia and MDS, luspatercept-aamt decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis in mice.

• REBLOZYL is an erythroid maturation agent indicated for the treatment of: • Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions ( 1.1 ). • Anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions ( 1.2 ).ICD-10: D64.9

• None. None ( 4 ).contraindicated

• Beta thalassemia: The recommended starting dose is 1 mg/kg once every 3 weeks by subcutaneous injection. Increase dose if patient has no reduction in RBC transfusion burden to a maximum of 1.25 mg/kg ( 2.1 ). • Myelodysplastic Syndromes: The recommended starting dose is 1 mg/kg once every 3 weeks by subcutaneous injection. o For ESA-naïve MDS, increase dose to maintain patient’s hemoglobin concentrations within the target range of 10 g/dL to 12 g/dL to a maximum of 1.75 mg/kg ( 2.2 ). o For ESA-refractory or intolerant MDS, increase dose if patient is not RBC transfusion-free to a maximum of 1.75 mg/kg ( 2.2 ). • Review hemoglobin (Hgb) results prior to each administration ( 2.1 , 2.2 ). • See full prescribing information for preparation and administration instructions ( 2.3 ). 2.1 Recommended Dosage for Beta Thalassemia The recommended starting dose of REBLOZYL is 1 mg/kg once every 3 weeks by subcutaneous injection for patients with beta thalassemia. Prior to each REBLOZYL dose, review the patient’s hemoglobin and transfusion record. Titrate the dose based on responses according to Table 1. Interrupt treatment for adverse reactions as described in Table 2. Discontinue REBLOZYL if no response as described in Table 1 , or if unacceptable toxicity occurs at any time as described in Table 2 . If a planned administration of REBLOZYL is delayed or missed, administer REBLOZYL as soon as possible and continue dosing as prescribed, with at least 3 weeks between doses. Dose Modifications for Response Assess and review hemoglobin results prior to each administration of REBLOZYL.

• Thrombosis/Thromboembolism: Increased risk in patients with beta thalassemia. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly ( 5.1 ). • Hypertension: Monitor blood pressure (BP) during treatment. Initiate anti-hypertensive treatment if necessary ( 5.2 ). • Extramedullary Hematopoietic (EMH) Masses: Increased risk in patients with beta thalassemia. Monitor patients for symptoms and signs or complications resulting from the EMH masses. Treat according to clinical guidelines and discontinue treatment in case of serious complications due to EMH masses ( 5.3 ). • Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception ( 5.4 , 8.1 , 8.3 ). 5.1 Thrombosis/Thromboembolism In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. Reported TEEs included deep vein thromboses, pulmonary embolus, portal vein thrombosis, and ischemic strokes. Patients with known risk factors for thromboembolism, e.g. splenectomy or concomitant use of hormone replacement therapy, may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients with beta thalassemia at increased risk of TEE. Monitor patients receiving REBLOZYL for signs and symptoms of thromboembolic events and institute treatment promptly. 5.2 Hypertension Hypertension was reported in 63/554 (11.4%) of REBLOZYL-treated patients.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Thrombosis/Thromboembolism [see Warnings and Precautions ( 5.1 )] • Hypertension [see Warnings and Precautions ( 5.2 )] • Extramedullary Hematopoietic Masses [see Warnings and Precautions ( 5.3 )] The most common (>10%) adverse reactions were fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, COVID-19, edema peripheral, hypertension, and hypersensitivity ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-888-423-5436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the WARNINGS AND PRECAUTIONS reflect exposure to REBLOZYL as a single agent administered across a range of doses (0.125 mg/kg to 1.75 mg/kg) in 571 patients in 4 trials. Beta Thalassemia The safety of REBLOZYL in patients with beta thalassemia was evaluated in the BELIEVE trial [see Clinical Studies ( 14.1 )] . Key eligibility criteria included adult patients with beta thalassemia (with the exception of patients with hemoglobin S or alpha-thalassemia disease) without major organ damage or recent DVT stroke and platelet counts less than or equal to 1000 x 10 9 /L.

Lactation: Advise not to breastfeed ( 8.2 ). 8.1 Pregnancy Risk Summary Based on findings in animal reproduction studies, REBLOZYL may cause fetal harm when administered to a pregnant woman . There are no available data on REBLOZYL use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, administration of luspatercept-aamt to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes including embryo-fetal mortality, alterations to growth, and structural abnormalities at exposures (based on area under the curve [AUC]) above those occurring at the maximum recommended human dose (MRHD) ( see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Luspatercept-aamt exhibited linear pharmacokinetics (PK) over the dose range of 0.2 to 1.25 mg/kg (0.2 to 1.25 times the recommended starting dosage) in patients with beta thalassemia, and from 0.125 mg/kg to 1.75 mg/kg (0.125 to 1.75 times the recommended starting dosage) in patients with MDS. The geometric mean (% coefficient of variation [%CV]) steady-state AUC at the starting dose of 1 mg/kg was 126 (35.9%) day•µg/mL for patients with beta thalassemia and 154 (37.4%) day•µg/mL for patients with MDS.

• Nov 8, 2019BLABLA761136Celgene Corp

1. 1Death2149.3%
2. 2Off Label Use1607.0%
3. 3Haemoglobin Decreased1355.9%
4. 4Fatigue1275.5%
5. 5Drug Ineffective964.2%
6. 6Product Storage Error853.7%
7. 7Weight Decreased813.5%
8. 8Dizziness763.3%
9. 9Dyspnoea672.9%
10. 10Fall632.7%
11. 11Myelodysplastic Syndrome622.7%
12. 12Asthenia542.3%
13. 13Weight Increased482.1%
14. 14Hypertension472.0%
15. 15Headache452.0%

The 10 most recently updated of 66 ClinicalTrials.gov registrations naming Luspatercept as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
  Recruiting · Phase 2 · Interventional · 2,000 enrolled · National Cancer Institute (NCI)
  NCT05564390updated 2026-06-11
• Luspatercept vs Epoetin in Treating Poor Erythroid Engraftment for Hematological Malignancies
  Not yet recruiting · Phase 2 · Phase 3 · Interventional · 90 enrolled · Nanfang Hospital, Southern Medical University
  NCT07636486updated 2026-06-09
• A Pilot, Open-Label Study of Luspatercept for Patients With Lower Risk Myelodysplastic Syndromes (MDS)
  Active not recruiting · Phase 2 · Interventional · 10 enrolled · M.D. Anderson Cancer Center
  NCT06113302updated 2026-06-08
• Luspatercept Plus CsA vs CsA for the Treatment of Newly Diagnosed Non-Transfusion-Dependent NSAA
  Withdrawn · Phase 4 · Interventional · 0 enrolled · Peking Union Medical College Hospital
  NCT06424639updated 2026-06-04
• A Real-World Study to Evaluate Luspatercept in Adults With Transfusion-Dependent Beta-Thalassemia in the Middle East
  Recruiting · Observational · 200 enrolled · Bristol-Myers Squibb
  NCT07215975updated 2026-06-02
• A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
  Recruiting · Phase 3 · Interventional · 665 enrolled · Celgene
  NCT04064060updated 2026-05-28
• Treatment Patterns and Outcomes in Patients With Lower-risk Myelodysplastic Syndromes Treated With Luspatercept in China
  Completed · Observational · 88 enrolled · Bristol-Myers Squibb
  NCT07073690updated 2026-05-19
• A Trial Comparing Three Different Treatment Options for Adults With Low-Risk Myelodysplasia and Anemia (A MyeloMATCH Treatment Trial)
  Not yet recruiting · Phase 2 · Interventional · 270 enrolled · National Cancer Institute (NCI)
  NCT07463820updated 2026-05-13
• Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms
  Active not recruiting · Phase 2 · Interventional · 6 enrolled · H. Lee Moffitt Cancer Center and Research Institute
  NCT05732961updated 2026-05-05
• A Study to Evaluate the Efficacy, Drug Levels and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Chinese and Japanese Participants With Ring Sideroblasts Who Require Red Blood Cell Transfusions
  Completed · Phase 2 · Interventional · 30 enrolled · Celgene
  NCT04477850updated 2026-05-05

Frequently asked questions

How does Luspatercept work?

Luspatercept-aamt is a recombinant fusion protein that binds several endogenous TGF-β superfamily ligands, thereby diminishing Smad2/3 signaling. In models of β-thalassemia and MDS, luspatercept-aamt decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis in mice.

What is Luspatercept used for?

According to FDA labeling, Luspatercept carries indications including: REBLOZYL is an erythroid maturation agent indicated for the treatment of: • Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions ( 1.1 ). • Anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions ( 1.2 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Luspatercept?

Luspatercept is classified as Other antianemic preparations, Erythroid Maturation Agent, Fusion Protein Interactions, Increased Erythroid Cell Production.

What are the brand names for Luspatercept?

Luspatercept is marketed under brand names including Reblozyl.

What are the contraindications for Luspatercept?

Luspatercept labeling lists contraindications including: None. None ( 4 ).. Always consult the full prescribing information and a clinician.