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

Abstract

β-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 β-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 β-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.

• Authors: Antonio Piga, Silverio Perrotta, Maria Rita Gamberini, Ersi Voskaridou, Angela Melpignano, Aldo Filosa, Vincenzo Caruso, Antonello Pietrangelo, Filomena Longo, Immacolata Tartaglione, Caterina Borgna-Pignatti, Xiaosha Zhang, Abderrahmane Laadem, Matthew L Sherman, Kenneth M Attie
• Journal: Blood (Blood) Vol. 133 Issue 12 Pg. 1279-1289 (03 21 2019) ISSN: 1528-0020 [Electronic] United States
• PMID: 30617198 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by The American Society of Hematology.

Chemical References

• Hemoglobins
• Immunoglobulin Fc Fragments
• Recombinant Fusion Proteins
• Activins
• luspatercept
• Activin Receptors, Type II

Topics

• Activin Receptors, Type II
• Activins (therapeutic use)
• Adult
• Erythrocyte Transfusion (statistics & numerical data)
• Female
• Follow-Up Studies
• Hemoglobins (analysis)
• Humans
• Immunoglobulin Fc Fragments (therapeutic use)
• Male
• Middle Aged
• Prognosis
• Recombinant Fusion Proteins (therapeutic use)
• Young Adult
• beta-Thalassemia (drug therapy)