What are the treatment options for beta-thalassemia major and the major hemoglobinopathies?

Updated: Nov 26, 2019
  • Author: Joseph E Maakaron, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Patients with beta-thalassemia major and the major hemoglobinopathies associated with sickle hemoglobin (Hb) usually require medical attention at frequent intervals for the treatment of anemia, infection, pain, and leg ulcers because of the serious nature of these illnesses. Conversely, many of the other hereditary abnormalities have minimal or no clinical manifestations; the patient requires only reassurance.

Patients with beta-thalassemia major and the major hemoglobinopathies associated with sickle hemoglobin (Hb) usually require medical attention at frequent intervals for the treatment of anemia, infection, pain, and leg ulcers because of the serious nature of these illnesses. Conversely, many of the other hereditary abnormalities have minimal or no clinical manifestations; the patient requires only reassurance.

Luspatercept, an erythroid maturation agent, is approved for anemia in adults with beta thalassemia who require regular red blood cell transfusions. The drug is a recombinant fusion protein that diminishes Smad2/3 signaling by binding several endogenous TGF-beta superfamily ligands. In a model of beta thalassemia, luspatercept decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis. 

Approval of luspatercept was based on the BELIEVE phase 3 clinical trial that included adults with beta thalassemia who require regular RBC transfusions (defined as 6-20 RBC units per 24 weeks, with no transfusion-free period greater than 35 days during that period). Patients (n=336) were randomized 2:1 to receive luspatercept (n=224) or placebo (n=112) at a starting dose of 1 mg/kg SC every 21 days for up to 48 weeks. In the patients who received luspatercept, 21.4% achieved a 33% or greater reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) during weeks 13-24 after randomization, compared with 4.5% (n=5) in the placebo arm (risk difference [95% CI]: 17.0 [10.4, 23.6], P< 0.0001). [15]


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