b-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with b-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (‡4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for ‡5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of ‡1.5 g/dL from baseline for ‡14 consecutive days (without RBC transfusions) for non–transfusion-dependent patients or RBC transfusion burden reduction ‡20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non–transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ‡1.5 g/dL over ‡14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved ‡20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of b-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409.

Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with b-thalassemia

Piga A.
First
;
Longo F.;
2019-01-01

Abstract

b-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with b-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (‡4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for ‡5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of ‡1.5 g/dL from baseline for ‡14 consecutive days (without RBC transfusions) for non–transfusion-dependent patients or RBC transfusion burden reduction ‡20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non–transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ‡1.5 g/dL over ‡14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved ‡20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of b-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409.
2019
133
12
1279
1289
http://www.bloodjournal.org/content/bloodjournal/133/12/1279.full.pdf
Activin Receptors, Type II; Activins; Adult; Erythrocyte Transfusion; Female; Follow-Up Studies; Hemoglobins; Humans; Immunoglobulin Fc Fragments; Male; Middle Aged; Prognosis; Recombinant Fusion Proteins; Young Adult; beta-Thalassemia
Piga A.; Perrotta S.; Gamberini M.R.; Voskaridou E.; Melpignano A.; Filosa A.; Caruso V.; Pietrangelo A.; Longo F.; Tartaglione I.; Borgna-Pignatti C.; Zhang X.; Laadem A.; Sherman M.L.; Attie K.M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1731507
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