SOHO State of the Art and Next Questions: Treatment of Higher-Risk Myelodysplastic Syndromes

Higher-risk myelodysplastic syndromes (MDS) carry a dismal prognosis with rapid disease progression, disease-related complications that impact quality of life, high risk of transformation to acute myeloid leukemia (AML), and poor long-term survival. Higher-risk disease is determined by a number of factors including the depth and type of cytopenias, percentage of myeloblasts occupying the bone marrow, cytogenetic abnormalities, and increasingly also by the presence of higher-risk molecular alterations. In addition to disease characteristics, a patient's performance status and degree of co-morbidity strongly influence treatment decisions and clinical outcomes. A critical first step in the management of patients with higher-risk MDS is evaluating eligibility for allogeneic hematopoietic stem cell transplant (HCT), which currently remains the only curative therapy, and is available to an ever-increasing number of patients. Outside of stem cell transplant, treatment with hypomethylating agent chemotherapy, azacitidine or decitabine, remains the cornerstone of therapy with improvements in overall survival and reduced transformation to AML; however, these approaches are palliative in nature and outcomes remain very poor overall. With a deepening understanding of disease pathophysiology has come a burgeoning array of novel targeted therapies that are currently in pre-clinical and early phase clinical trials offering hope for new treatment options for this malignancy.