Luspatercept

What it is and how it works

Mechanism of Action 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. Luspatercept-aamt promoted erythroid maturation through differentiation and increasing the percentage of late-stage erythroid precursors (normoblasts) in the bone marrow of mice and increased erythroid precursors in humans, thereby increasing erythropoiesis.

Indications

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 . • 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 . • Anemia failing an erythropoiesis stimulating agent and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) . • Limitations of Use: REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia . Beta Thalassemia REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

Dosage and administration (summary)

• 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 . • 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 . o For ESA-refractory or intolerant MDS, increase dose if patient is not RBC transfusion-free to a maximum of 1.75 mg/kg . • Review hemoglobin (Hgb) results prior to each administration ( 2.1 , 2.2 ).

Contraindications

None. None .

Warnings and precautions

• Thrombosis/Thromboembolism: Increased risk in patients with beta thalassemia. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly . • Hypertension: Monitor blood pressure (BP) during treatment. Initiate anti-hypertensive treatment if necessary . • 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 .

Pregnancy

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.

Storage and supply

Storage Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze.

Source: Luspatercept (Reblozyl) — US FDA prescribing information, 2026-02-27, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.