Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 630
Erythropoiesis maturating agents
ОглавлениеThe TGF‐b superfamily includes a large number of proteins, such as activins, growth differentiation factors (GDFs), and bone morphogenetic proteins (BMPs), mainly secreted by hematopoietic and mesenchymal stem cells, which inhibit terminal erythroid differentiation in erythroblasts by induction of apoptosis and cell‐cycle arrest. Sotatercept and luspatercept are recombinant fusion proteins that bind the TGF‐b ligands, reducing their activity and promoting erithroblast maturation. Recently a phase 3 trial proved that luspatercept treatment was effective in reducing transfusion burden in lower‐risk MDS with ringed sideroblasts or SF3B1 mutations refractory or ineligible for ESA. Transfusion independence for eight weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group. The most common adverse events included fatigue, diarrhoea, asthenia, nausea, and dizziness. Pending regulatory approval by FDA and EMA, these agents could be a valid second‐line option for this group of patients