Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

Current Opinion in Hematology
Amer M ZeidanRami S Komrokji

Abstract

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 ...Continue Reading

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Citations

Aug 22, 2015·Expert Review of Anticancer Therapy·Abdallah Abou ZahrAmer M Zeidan
Oct 16, 2014·European Journal of Haematology·Je-Hwan LeeYoung-Don Joo
Jul 2, 2015·Current Hematologic Malignancy Reports·Daniel A Roberts, David P Steensma
Feb 27, 2016·Leukemia & Lymphoma·Gabriel A RiveraPeter L Greenberg
Aug 4, 2016·Expert Opinion on Emerging Drugs·Amer M ZeidanRami Komrokji
Jun 2, 2016·American Society of Clinical Oncology Educational Book·Rami S Komrokji
Feb 23, 2019·Journal of Cellular and Molecular Medicine·Xiang-Mei WenJun Qian
Jan 13, 2015·Current Opinion in Hematology·Amer M ZeidanRami S Komrokji

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