Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases that are prognostically stratified into lower-risk (LR-MDS) and higher-risk MDS on the basis of the International Prognostic Scoring System (eg, IPSS, revised IPSS, and molecular IPSS). Anemia is a hallmark of MDS and can lead to worsening of preexisting comorbidities, long-term RBC transfusion dependence, and profound fatigue. Although RBC transfusion support provides rapid relief of anemia-associated symptoms, it also carries a risk of iron overload and alloimmunization, and is associated with a decreased quality of life. Thus, many clinical trials and treatment strategies for LR-MDS focus on RBC transfusion independence (RBC-TI) as a primary end point. In this review, we discuss the updated treatment paradigm for anemia in LR-MDS. Novel insights in the pathogenesis of MDS and results from positive phase III clinical trials in LR-MDS have led to a growing number of therapeutic options (eg, luspatercept and imetelstat). Imetelstat was recently added as a new agent for patients who are refractory/resistant or ineligible for erythropoiesis-stimulating agent treatment on the basis of the randomized phase III IMerge trial, showing that imetelstat led to the primary end point of RBC-TI for ≥8 weeks in 40% of patients compared with 15% in patients receiving placebo. However, future clinical trials are needed to investigate the optimal sequencing of different agents and the potential of improving efficacy using combination of therapeutic strategies in LR-MDS.
Hoff et al. (2025) studied this question.