Optimal sequencing of treatments for patients with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are characterized by chronic cytopenias and a high risk of transformation to acute myeloid leukemia. To date, only allogeneic stem cell transplantation has shown curative potential in MDS. The heterogeneous nature of MDS, and the paucity of randomized studies make individual therapeutic decisions, still largely based on the international prognostic scoring system, difficult.

In lower-risk MDS, recent advances include demonstration of a possible survival advantage with erythropoiesis stimulating agents, the role of lenalidomide in cases with del 5q (which lead to its approval in the treatment of lower-risk MDS with del 5q by the Food and Drug Administration), and recognition of the importance of iron overload on prognosis. In higher-risk patients, progress has come from the use of reduced intensity conditioning allogeneic SCT in elderly patients, and from results obtained with the hypomethylating agents azacytidine and decitabine, leading to their approval for the treatment of symptomatic MDS by the Food and Drug Administration. In particular, results of a phase III trial show a significant survival benefit for azacytidine over conventional treatments in higher-risk MDS. This is the first time a drug demonstrates a survival impact in higher-risk MDS.

We review these recent advances in this paper.