Περίληψη:
BACKGROUND Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was −348 μg per liter (95% confidence interval, −517 to −179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. © 2020 Massachusetts Medical Society.
Συγγραφείς:
Domenica Cappellini, M.
Viprakasit, V.
Taher, A.T.
Georgiev, P.
Kuo, K.H.M.
Coates, T.
Voskaridou, E.
Liew, H.-K.
Pazgal-Kobrowski, I.
Forni, G.L.
Perrotta, S.
Khelif, A.
Lal, A.
Kattamis, A.
Vlachaki, E.
Origa, R.
Aydinok, Y.
Bejaoui, M.
Joy Ho, P.
Chew, L.-P.
Bee, P.-C.
Lim, S.-M.
Lu, M.-Y.
Tantiworawit, A.
Ganeva, P.
Gercheva, L.
Shah, F.
Neufeld, E.J.
Thompson, A.
Laadem, A.
Shetty, J.K.
Zou, J.
Zhang, J.
Miteva, D.
Zinger, T.
Linde, P.G.
Sherman, M.L.
Hermine, O.
Porter, J.
Piga, A.
BELIEVE Investigators
Λέξεις-κλειδιά:
luspatercept; placebo; activin receptor 2; antianemic agent; ferritin; fusion protein; immunoglobulin Fc fragment; luspatercept, adult; adverse outcome; aged; arthralgia; Article; beta thalassemia; bone pain; controlled study; dizziness; double blind procedure; drug efficacy; drug safety; female; human; hypertension; hyperuricemia; major clinical study; male; outcome assessment; phase 3 clinical trial; priority journal; randomized controlled trial; adolescent; beta thalassemia; blood; clinical trial; erythrocyte transfusion; genetics; intention to treat analysis; least square analysis; middle aged; multicenter study; odds ratio; splenectomy; young adult, Activin Receptors, Type II; Adolescent; Adult; Aged; beta-Thalassemia; Double-Blind Method; Erythrocyte Transfusion; Female; Ferritins; Hematinics; Humans; Immunoglobulin Fc Fragments; Intention to Treat Analysis; Least-Squares Analysis; Male; Middle Aged; Odds Ratio; Recombinant Fusion Proteins; Splenectomy; Young Adult
