Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study

• Published in: The lancet oncology 2017-10, Vol.18 (10), p.1338-1347
• Main Authors: Platzbecker, Uwe, Germing, Ulrich, Götze, Katharina S, Kiewe, Philipp, Mayer, Karin, Chromik, Jörg, Radsak, Markus, Wolff, Thomas, Zhang, Xiaosha, Laadem, Abderrahmane, Sherman, Matthew L, Attie, Kenneth M, Giagounidis, Aristoteles
• Format: Article
• Language: English
• Subjects: Activins - administration & dosage; Activins - adverse effects; Adult; Aged; Anemia; Anemia - drug therapy; Anemia - etiology; Anemia - mortality; Blood; Blood transfusion; Classification; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Fusion protein; Germany; Growth factors; Hemoglobin; Humans; Immunoglobulin Fc Fragments - administration & dosage; Immunoglobulin Fc Fragments - adverse effects; Kaplan-Meier Estimate; Leukemia; Ligands; Male; Maximum Tolerated Dose; Middle Aged; Motivation; Mutation; Myalgia; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - complications; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - mortality; Pain; Patients; Product development; Prognosis; Proportional Hazards Models; Prospective Studies; Pruritus; Quality of life; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - adverse effects; Risk Assessment; Severity of Illness Index; Sideroblasts; Survival Analysis; Time Factors; Titration; Transforming growth factor-b; Treatment Outcome; Tumors
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(17)30615-0

Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes. In this phase 2, multicentre, open-label, dose-finding study (PACE-MDS), with long-term extension, eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low or intermediate 1 risk myelodysplastic syndromes or non-proliferative chronic myelomonocytic leukaemia (white blood cell count