Although hypomethylating agents (HMAs) significantly improve outcomes in myelodysplastic syndromes (MDS), only half the patients achieve objective responses, and most responders lose response within 1–2 years. Azacitidine prolongs survival by a median of only 9.5 months. Failure of HMA therapy is associated with a very dismal prognosis. Therefore, novel therapeutic approaches are clearly needed.
The sequential use of the alternative HMA after failure of first line HMA is associated with modest efficacy. The improved understanding of the biologic underpinnings of the disease have opened the door to study investigational agents that target disrupted molecular pathways critical to the pathogenesis of MDS. Combination treatment strategies using an azacitidine backbone are demonstrating promising early results. Expanding the applicability of allogeneic stem cell transplantation (alloSCT), the only curative modality, by reducing toxicity and relapse rates is another area of active research.
Sequential switching to the alternative HMA, clinical trials of novel targeted therapies, azacitidine-based combination therapeutic strategies, and improvements in the alloSCT platform are the main directions in improving outcomes of MDS post HMA failure.
aDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
bDepartment of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute
cDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
Correspondence to Amer M. Zeidan, Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, CRB1 building, Room 186, Baltimore, MD 21287, USA. Tel: +1 410 614 4459; fax: +1 410 955 0185; e-mail: email@example.com