BACKGROUND:
Patients with anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. and lower-risk myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor growth factor: A substance made by the body that stimulates the bone marrow to produce blood cells. Some growth factors are man-made in the laboratory and used for treating low blood counts. These include red blood cell growth factors called erythropoietin (EPO) and darbepoetin, and white blood cell growth… β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study.
METHODS:
In a double-blind, placebo placebo: A placebo is an inactive pill, liquid, or powder that has no treatment value. -controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System International Prognostic Scoring System: A system that turns patient data into a score. The score tells how quickly a myelodysplastic syndrome (MDS) case is progressing and helps predict what may happen with the patient's MDS in the future. Also called IPSS. ) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence transfusion independence: No longer needing any type of blood transfusion. for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48.
RESULTS:
Of the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspatercept-associated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time.
CONCLUSIONS:
Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory refractory: Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments. to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.).