Use of Oral Hypomethylating Agents for the Treatment of Myelodysplastic Syndromes

Introduction Myelodysplastic syndromes (MDS) are genomically complex clonal hematopoietic stem cell neoplasms leading to myelodysplasia and ineffective hematopoiesis.1,2 MDS is a disease of older age, clinically manifesting as symptomatic cytopenias with an added propensity for transformation to acute myeloid leukemia (AML).3 The treatment of MDS is based on a risk-adapted approach per the International Prognostic Scoring System (IPSS)4 or the modified IPSS-R.5 Allogeneic stem cell transplantation (ASCT) is the only curative strategy, but most patients are not eligible due to their age or other comorbidities.6 In these patients, hypomethylating agents (HMA, either decitabine or azacitidine) are the mainstay of therapy to either alleviate cytopenias or impede disease progression. 7 Decitabine (DEC) and azacitidine (AZA) are approved to treat patients with MDS, including previously treated and untreated, de novo, and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk IPSS groups.7