For the anemia of lower-risk myelodysplastic syndromes (MDS) with ring sideroblasts — the disorder underlying most acquired sideroblastic anemia — two agents have reshaped care beyond erythropoiesis-stimulating agents (ESAs).
Luspatercept (Reblozyl), an erythroid maturation agent that traps TGF-β superfamily ligands to improve late-stage red-cell production, first proved itself in the MEDALIST trial, achieving transfusion independence in transfusion-dependent, ESA-refractory patients with ring sideroblasts. Its role then expanded: the COMMANDS trial showed luspatercept superior to epoetin alfa as first-line therapy in ESA-naïve lower-risk MDS, leading to a broadened approval — so it is now an option before ESAs, not just after them.
The newer addition is imetelstat (Rytelo), a first-in-class telomerase inhibitor approved in 2024 for transfusion-dependent lower-risk MDS in patients who have not responded to or are ineligible for ESAs (IMerge trial). By targeting the malignant clone rather than simply stimulating erythropoiesis, it offers a mechanistically distinct option, at the cost of dose-dependent cytopenias requiring monitoring.
Further reading: luspatercept MEDALIST (Fenaux et al., NEJM 2020) and COMMANDS (Platzbecker et al., Lancet 2023); imetelstat IMerge and 2024 approval.