New agents for the treatment of myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cell disorders commonly characterized by a hypercellular and dysplastic bone marrow, cytopenias resulting from impaired peripheral blood cell production, and an increased risk of leukemic transformation. Currently, azacitidine, decitabine, and lenalidomide are approved by the US Food and Drug Administration for the treatment of MDS. The DNA methyltransferase (DNMT) inhibitors such as azacitidine and decitabine have demonstrated the ability to alter the natural history of disease and thus prolong time to leukemic transformation. In addition, azacitidine has shown the capacity to extend survival compared with the previous gold standard of conventional care regimens. Recently, decitabine has been shown to be well tolerated with a toxicity profile expected for this class of agent. Recent studies also suggest that decitabine may result in additional improvements in response. As more is learned about the mechanism of hypomethylating agents, new roles are emerging for decitabine in combination therapy for MDS. The third agent, lenalidomide, is a thalidomide analogue with significant activity in a subset of patients with low-risk MDS, anemia and chromosome 5 alterations. Several other agents are being evaluated in MDS. This review summarizes the existing clinical experience on DNMT inhibitors and other drugs for the treatment of MDS. (Korean J Med 76:121-125, 2009)