Evolving Treatment Strategies for Elderly Leukemia Patients with IDH Mutations.
Evolving Treatment Strategies for Elderly Leukemia Patients with IDH Mutations.
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DOI：
10.3390/cancers10060187
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发表时间：
2018-06-06
期刊：
影响因子：
5.2
通讯作者：
DiNardo CD
中科院分区：
文献类型：
--
作者：
Buege MJ;DiPippo AJ;DiNardo CD
急性髓性白血病（AML）是一种使人衰弱和危及生命的疾病，特别是老年患者，占诊断的50%以上。四十多年来，AML的标准诱导治疗与强化细胞毒性化疗保持不变。然而，对于大多数患者，标准治疗仍然有其缺点，特别是对于老年患者，他们可能无法耐受强化细胞毒性化疗的并发症。针对靶向和替代疗法开发的新研究开创了AML治疗的新时代。对于近20%的异柠檬酸脱氢酶1或2（IDH 1/2）突变的诊断，潜在的治疗选择已经经历了从强化细胞毒性化疗到单独靶向治疗或与低强度化疗联合的范式转变。2017年，FDA批准的第一个IDH 2抑制剂是恩西地尼。此外，IDH 1抑制剂正在进行中的临床研究中，口服BCL-2抑制剂venetoclax在这部分患者中显示出初步疗效。这些新工具旨在改善IDH突变AML老年患者的结局并改变治疗模式。然而，如何最好地将这些药物纳入标准做法的挑战仍然存在。
Acute myeloid leukemia (AML) is a debilitating and life-threatening condition, especially for elderly patients who account for over 50% of diagnoses. For over four decades, standard induction therapy with intensive cytotoxic chemotherapy for AML had remained unchanged. However, for most patients, standard therapy continues to have its shortcomings, especially for elderly patients who may not be able to tolerate the complications from intensive cytotoxic chemotherapy. New research into the development of targeted and alternative therapies has led to a new era in AML therapy. For the nearly 20% of diagnoses harboring a mutation in isocitrate dehydrogenase 1 or 2 (IDH1/2), potential treatment options have undergone a paradigm shift away from intensive cytotoxic chemotherapy and towards targeted therapy alone or in combination with lower intensity chemotherapy. The first FDA approved IDH2 inhibitor was enasidenib in 2017. In addition, IDH1 inhibitors are in ongoing clinical studies, and the oral BCL-2 inhibitor venetoclax shows preliminary efficacy in this subset of patients. These new tools aim to improve outcomes and change the treatment paradigm for elderly patients with IDH mutant AML. However, the challenge of how to best incorporate these agents into standard practice remains.
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