Welcome to Managing MDS. I am Dr. Shyamala Navada and I would like to briefly discuss how to treat refractory anemia with ring sideroblasts.
The treatment of patients with refractory anemia with ring sideroblasts includes supportive care strategies used for lower-risk MDS patients and includes the use of erythropoiesis stimulating agents, also known as ESAs, transfusions, and iron chelation when needed. Commercially available ESAs include recombinant human erythropoietin and darbepoetin. Response rates in lower-risk MDS patients range from 30% to 60% with a median duration of response being about two years. Patients are more likely to respond to ESA therapy if they have a low transfusion burden of less than two units a month and a lower baseline serum EPO level of less than 500 IU/mL. Most responses to ESAs occur within eight weeks of treatment and close monitoring of hemoglobin is required to avoid increases of greater than 12. Weekly doses of 40,000 units of recombinant human erythropoietin or 150 to 300 mcg of darbepoetin yield erythroid responses in 50% to 60% of patients. Meta-analysis have not demonstrated any significant difference between recombinant human erythropoietin versus darbepoetin, while there appears to be a benefit with the addition of G-CSF to ESAs, particularly in patients with refractory anemia with ring sideroblasts. Luspatercept is a recombinant fusion protein that binds TGF beta superfamily ligands, increasing hemoglobin levels by targeting a pathway fundamentally distinct from EPO. The MEDALIST trial was a phase 3, randomized, double-blind, placebo-controlled study assessing the efficacy of luspatercept versus placebo in lower-risk patients with MDS with ring sideroblasts who were refractory, intolerant, or ineligible for an ESA and were red blood cell transfusion dependent. The primary endpoint was transfusion independence for eight weeks or longer during weeks 1 through 24, which was achieved in 37.9% of the patients receiving luspatercept compared to 13% in the placebo group. This drug has been approved in beta thalassemia and is currently being evaluated by the FDA for an MDS indication.
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