Department of Internal Medicine, Section of Hematology, Yale School of Medicine, 300 George Street, New Haven, CT, 06510-3222, USA.
Target Oncol. 2017 Aug;12(4):413-447. doi: 10.1007/s11523-017-0503-8.
Acute myeloid leukemia (AML) is one of the best studied malignancies, and significant progress has been made in understanding the clinical implications of its disease biology. Unfortunately, drug development has not kept pace, as the '7+3' induction regimen remains the standard of care for patients fit for intensive therapy 40 years after its first use. Temporal improvements in overall survival were mostly confined to younger patients and driven by improvements in supportive care and use of hematopoietic stem cell transplantation. Multiple forms of novel therapy are currently in clinical trials and are attempting to bring bench discoveries to the bedside to benefit patients. These novel therapies include improved chemotherapeutic agents, targeted molecular inhibitors, cell cycle regulators, pro-apoptotic agents, epigenetic modifiers, and metabolic therapies. Immunotherapies in the form of vaccines; naked, conjugated and bispecific monoclonal antibodies; cell-based therapy; and immune checkpoint inhibitors are also being evaluated in an effort to replicate the success seen in other malignancies. Herein, we review the scientific basis of these novel therapeutic approaches, summarize the currently available evidence, and look into the future of AML therapy by highlighting key clinical studies and the challenges the field continues to face.
急性髓系白血病（AML）是研究得最好的恶性肿瘤之一，在理解其疾病生物学的临床意义方面取得了重大进展。不幸的是，药物开发并没有跟上步伐，因为“7+3”诱导方案仍然是适合强化治疗的患者的标准治疗方法，自首次使用以来已经过去了 40 年。总体生存时间的改善主要局限于年轻患者，这是由于支持性护理的改善和造血干细胞移植的使用推动的。目前有多种新型疗法正在临床试验中，并试图将实验室发现转化为临床应用，使患者受益。这些新型疗法包括改良的化疗药物、靶向分子抑制剂、细胞周期调节剂、促凋亡剂、表观遗传学修饰剂和代谢疗法。免疫疗法的形式有疫苗、裸抗体、偶联抗体和双特异性单克隆抗体、基于细胞的疗法和免疫检查点抑制剂也在评估中，以期复制在其他恶性肿瘤中看到的成功。在此，我们综述了这些新型治疗方法的科学基础，总结了目前可用的证据，并通过突出关键的临床研究和该领域继续面临的挑战，探讨 AML 治疗的未来。
