Overview
11 DESCRIPTION Luspatercept-aamt is an erythroid maturation agent. Luspatercept-aamt is a receptor fusion protein consisting of a modified extracellular domain of the human activin receptor type IIB linked to a human IgG1 Fc domain with a calculated molecular mass of approximately 76 kD. Luspatercept is produced in Chinese hamster ovary cells by recombinant DNA technology.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. 12.
Indications
- 1 INDICATIONS AND USAGE 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 ).
Common Doses
- 1 mg
- 1.25 mg
- 10 g
- 12 g
Dosage
2 DOSAGE AND ADMINISTRATION • 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 ).
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 ).
Side Effects
- 6 ADVERSE REACTIONS 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 ).
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.