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Activin Receptor II Ligand Traps: New Treatment Paradigm for Low-Risk MDS

Journal Title: 
Current Hematologic Malignancy Report
Primary Author: 
Komrokji RS
Komrokji RS
Original Publication Date: 
Saturday, June 15, 2019


Alleviating cytopenias, namely anemia, is the main goal of therapy in lower-risk myelodysplastic syndromes (MDS). Current available treatment options remain limited. We review the role of TGF-B pathway in MDS, the current available data on luspatercept and sotatercept development.


TGF-B pathway is overactivated in MDS contributing to observed myelosuppression. SMADs, the downstream proteins of TGF-B pathway, are upregulated. GDF-11 is a negative regulator of terminal erythroid differentiation and an activin receptor ligand. Sotatercept and luspatercept are fusion ligand trap novel agents for activin II receptors A and B, respectively. Early promising results have been reported with those novel agents for treating anemia in lower-risk MDS patients, and higher responses were observed among patients with ring sideroblasts and SF3B1 mutation. A phase III randomized clinical trial with luspatercept was recently conducted. Activin receptor II ligand traps may represent a new paradigm for anemia treatment in MDS.

Bone Marrow Disease(s): 
  • myelodysplastic syndromes (MDS)
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