Abstract Body

The most frequently encountered cytopenia in IPSS-R lower risk MDS is anemia, which is responsible for the poor quality of life and clinical complications of these patients. While therapy with erythropoietic stimulating agents ( ESAs) is active in the vast majority of cases if rightly selected, some patients do not respond, or become irresponsive to ESAs. Novel agents with very different mode of action show promising clinical results in anemic LR-MDS refractory/relapsed after ESAs. Luspatercept, a TGFbeta family ligand-trap induces nearly 50% of RBC transfusion independence in MDS with ring sideroblasts ( RS), but it has been shown to be active also in transfusion dependent non-RS LR MDS both in first line and after failure of ESA treatment. The telomerase inhibitor imetelstat has shown efficacy and disease modifying activity in LR MDS ESA refractory or relapsed, who did not receive lenalidomide or hypomethylating agents. More recently, a randomized study vs placebo confirmed the activity of imetelstat in this setting, both in inducing RBC transfusion independence and in targeting the dysplastic clone. Another approach has been represented by the oral hypoxia–inducible factor (HIF) prolyl hydroxylase inhibitor roxadustat, tested in anemic LR- MDS pts (IPSS-R ≤4.5), non del(5q), low transfusion burden and endogenous EPO ≤400 U/L. This agent was also active in determining hematological improvement, mostrly in MDS-RS negative. Modulation of dose and schedule of hypomethylating agents, both injectable and in oral formulation is currently explored and preliminary results are positive.