LUSPATERCEPT |

Varthiya Aishwarya^*, Ritika Sud^**

^*Postgraduate Resident, Department of Medicine, Lady Hardinge Medical College, New Delhi

^**Professor, Department of Medicine, Lady Hardinge Medical College, New Delhi

INTRODUCTION:

Luspatercept is an FDA approved drug used to manage and treat anemia in patients who need regular blood cell transfusion in myelodysplastic syndrome, primary myelofibrosis and beta-thalassemia.

MECHANISM OF ACTION:

Luspatercept is a fusion protein consisting of the extracellular domain of activin receptor type 2B fusion protein and the Fc- part of human immunoglobulin G1 (IgG1). It blocks the transforming growth factor- Beta (TGF-beta) superfamily inhibitors to reduce SMAD2 and SMAD3 signaling. This activity prevents the activation of TGF-beta superfamily members involved, leading to ineffective erythropoiesis in late stage.

ADMINISTATION:

Luspatercept is given at 1mg/kg once every three weeks by subcutaneous injection into upper arm, thigh or abdomen. If RBC’s transfusion reduction is not met with two consecutive doses of luspatercept at the of 1mg/kg dose, increasing the dose to 1.25mg/kg can be considered. A patient who is not receiving transfusion therapy and demonstrates more than 2g/dl of hemoglobin levels within three weeks dose should be reduced.

ADVERSE EFFECTS:

The most common adverse events are fatigue, headache, myalgia, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, hypertension, hyperuricemia and hypersensitivity. It is not a substitute to blood transfusion in medical necessity. Bone pain, hyperuricemia and hypertension are considered to be grade 3 & 4 reaction and can result in decline of physical health.

INDICATIONS:

Luspatercept is an FDA- approved drug to be used to treat anemia in patients who need regular red blood transfusion in beta thalassemia, myelodysplastic syndrome with ring sideroblasts and thrombocytosis associated anemia. It is also indicated in patients who fail to respond to erythropoietin stimulating agents and have lower risk for ring sideroblasts.

CONTRAINDICATIONS:

No contraindication are directly associated at present with a good safety profile. Stimulating erythropoiesis can lead to hyper viscosity of the blood leading to thromboembolic events and hypertension. Therefore pregnant female, hypertensive patients and women on oral contraceptives pills and underlying blood conditions that can cause increased RBC’S counts should be considered and given other options.

MONITORING:

Hemoglobin and liver function test should be monitored before and after administration of luspatercept. It can be detected in the human serum with ELISA and western blotting.

TOXICITY:

Luspatercept due to its long-half life, toxicity is not significant. Dosing should be monitored according to hemoglobin levels and should not exceed 1.25mg/kg in the treatment of beta-thalassemia and 1.75 mg/kg in low risk MDS to avoid toxicity.

REFERENCES :

Patel B, Moosavi L. Luspatercept. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560635/