Active Treatment Strategies Improving Outcomes in Patients with Myelodysplastic Syndromes with the Deletion 5q Abnormality

Abstract Myelodysplastic syndromes (MDS) have undergone a therapeutic revolution in the past decade that has redefined treatment strategies for this disease. Patients with early-stage MDS who harbor a clonal chromosome 5q deletion (del[5q]) represent a distinct subset of MDS that is clinically, pathologically, and often prognostically distinct. While the vast majority of patients with MDS are red blood cell transfusion dependent, natural history of the disease varies from indolent (with a low-risk of leukemia evolution), in patients with isolated del(5q), to a high-risk of leukemia and poor survival in patients with a complex karyotype. Lenalidomide, which specifically targets the del(5q) clone, selectively suppresses the clone to yield transfusion independence and a cytogenetic response in approximately two thirds of patients, a response that is sustained for a median of 2.2 years. Features associated with a higher likelihood of transfusion independence include early treatment-related cytopenias and lower baseline transfusion needs, whereas the expectation for extended overall survival and freedom from leukemia evolution is greatest in cytogenetic responders. Future applications of lenalidomide will target patients with del(5q) with more advanced disease, will exploit the potentiation effects of lenalidomide's interaction with other agents, and will target novel pathways.