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.
Curr Opin Hematol. 2014 Mar;21(2):123-30. doi: 10.1097/MOH.0000000000000016.
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.
尽管低甲基化剂（HMAs）显著改善了骨髓增生异常综合征（MDS）的预后，但只有一半的患者获得客观反应，而且大多数反应者在 1-2 年内失去反应。阿扎胞苷通过中位数仅延长 9.5 个月的生存时间。HMA 治疗失败与预后极差相关。因此，显然需要新的治疗方法。
在一线 HMA 治疗失败后序贯使用替代 HMA 具有一定的疗效。对疾病生物学基础的深入理解为研究靶向 MDS 发病机制中关键分子途径的试验性药物开辟了道路。以阿扎胞苷为基础的联合治疗策略显示出有希望的早期结果。通过降低毒性和复发率，扩大唯一治愈方式——同种异体造血干细胞移植（alloSCT）的适用性是另一个积极研究的领域。
序贯转换为替代 HMA、新型靶向治疗的临床试验、基于阿扎胞苷的联合治疗策略以及 alloSCT 平台的改进是改善 HMA 失败后 MDS 结局的主要方向。
