[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents].

Abstract

Several novel myelodysplastic syndromes (MDS) treatment drugs are being developed, and luspatercept and oral hypomethylating medicines have already been licensed in the United States and other countries. Luspatercept is a ligand trap that inhibits SMAD2/3 signals by combining the extracellular domain of the activin type IIA receptor with the human immunoglobulin G1 Fc domain. In the phase 2 study for low-risk MDS, the hematological improvement-erythroid (HI-E) was found in 63% of patients, and in the phase 3 study for transfusion-dependent low-risk MDS with ring sideroblasts, 38% of patients achieved transfusion independence. A combination of oral decitabine with oral cedazuridine, an inhibitor of cytidine deaminase, which metabolizes decitabine, demonstrated pharmacological equivalence with intravenous decitabine and has overall response rates of 60% and 43% for high-risk MDS in phase 2 and 3 trials, respectively. Furthermore, oral azacitidine and its combination with oral cedazuridine have been under development.

• Authors: Kensuke Usuki
• Journal: [Rinsho ketsueki] The Japanese journal of clinical hematology (Rinsho Ketsueki) Vol. 63 Issue 9 Pg. 1099-1106 ( 2022) ISSN: 0485-1439 [Print] Japan
• PMID: 36198535 (Publication Type: Journal Article)

Chemical References

• Immunoglobulin Fc Fragments
• Ligands
• Recombinant Fusion Proteins
• Activins
• Decitabine
• luspatercept
• Activin Receptors, Type II
• Cytidine Deaminase
• Azacitidine

Topics

• Activin Receptors, Type II
• Activins (therapeutic use)
• Azacitidine (therapeutic use)
• Cytidine Deaminase
• Decitabine (therapeutic use)
• Humans
• Immunoglobulin Fc Fragments
• Ligands
• Myelodysplastic Syndromes (drug therapy)
• Recombinant Fusion Proteins
• Treatment Outcome