Buege Michael J, DiPippo Adam J, DiNardo Courtney D
Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2018 Jun 6;10(6):187. doi: 10.3390/cancers10060187.
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.
急性髓系白血病（AML）是一种使人衰弱且危及生命的疾病，对于占诊断病例50%以上的老年患者而言尤其如此。四十多年来，AML强化细胞毒性化疗的标准诱导疗法一直未变。然而，对大多数患者来说，标准疗法仍有其不足之处，特别是对于那些可能无法耐受强化细胞毒性化疗并发症的老年患者。针对靶向疗法和替代疗法的新研究开启了AML治疗的新时代。对于近20%诊断出异柠檬酸脱氢酶1或2（IDH1/2）发生突变的患者，潜在治疗方案已发生了范式转变，从强化细胞毒性化疗转向单独使用靶向疗法或与低强度化疗联合使用。2017年，首个获美国食品药品监督管理局（FDA）批准的IDH2抑制剂是恩杂鲁胺。此外，IDH1抑制剂正在进行临床研究，口服BCL-2抑制剂维奈托克在这部分患者中显示出初步疗效。这些新方法旨在改善治疗效果并改变IDH突变型老年AML患者的治疗模式。然而，如何将这些药物最佳地纳入标准治疗方案仍是一个挑战。
