Department of Leukemia, MD Anderson Cancer Center, Houston, Texas.
Cancer. 2021 Apr 15;127(8):1186-1207. doi: 10.1002/cncr.33477. Epub 2021 Mar 18.
The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. The notable subsets of AML include acute promyelocytic leukemia (APL), core-binding factor AML (CBF-AML), AML in younger patients fit for intensive chemotherapy, and AML in older/unfit patients (usually at the age cutoff of 60-70 years). We also consider within each subset whether the AML is primary or secondary (therapy-related, evolving from untreated or treated myelodysplastic syndrome or myeloproliferative neoplasm). In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80%. Treatment of CBF-AML with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin (GO) results in estimated 10-year survival rates of ≥75%. In younger/fit patients, the "3+7" regimen (3 days of daunorubicin + 7 days of cytarabine) produces less favorable results (estimated 5-year survival rates of 35%; worse in real-world experience); regimens that incorporate high-dose cytarabine, adenosine nucleoside analogs, and GO are producing better results. Adding venetoclax, FLT3, and IDH inhibitors into these regimens has resulted in encouraging preliminary data. In older/unfit patients, low-intensity therapy with hypomethylating agents (HMAs) and venetoclax is now the new standard of care. Better low-intensity regimens incorporating cladribine, low-dose cytarabine, and other targeted therapies (FLT3 and IDH inhibitors) are emerging. Maintenance therapy now has a definite role in the treatment of AML, and oral HMAs with potential treatment benefits are also available. In conclusion, AML therapy is evolving rapidly and treatment results are improving in all AML subsets as novel agents and strategies are incorporated into traditional AML chemotherapy. LAY SUMMARY: Ongoing research in acute myeloid leukemia (AML) is progressing rapidly. Since 2017, the US Food and Drug Administration has approved 10 drugs for different AML indications. This review updates the research and treatment pathways for AML.
急性髓系白血病（AML）的病理生理学研究取得了突破性进展，相关信息迅速转化为临床实践。经过 40 多年 AML 研究进展缓慢后，自 2017 年以来，美国食品和药物管理局已批准了 9 种药物用于不同的 AML 治疗适应症。在这篇综述中，我们详细介绍了 AML 研究和治疗方面的进展，并引用了自 2000 年以来英文文献中与 AML 研究和治疗相关的关键出版物。AML 的显著亚型包括急性早幼粒细胞白血病（APL）、核心结合因子 AML（CBF-AML）、适合强化化疗的年轻患者的 AML 以及年龄较大/不适合（通常在 60-70 岁截止年龄）的 AML。我们还考虑了每个亚组中 AML 是原发性还是继发性（治疗相关，从未治疗或治疗的骨髓增生异常综合征或骨髓增殖性肿瘤发展而来）。在 APL 中，全反式维甲酸和三氧化二砷联合治疗的 10 年估计生存率≥80%。氟达拉滨、高剂量阿糖胞苷和吉妥珠单抗奥佐米星（GO）联合治疗 CBF-AML 的 10 年估计生存率≥75%。在年轻/适合的患者中，“3+7”方案（3 天柔红霉素+7 天阿糖胞苷）的效果较差（估计 5 年生存率为 35%；实际经验更差）；包含高剂量阿糖胞苷、腺苷核苷类似物和 GO 的方案正在产生更好的结果。在这些方案中加入 venetoclax、FLT3 和 IDH 抑制剂已产生令人鼓舞的初步数据。在年龄较大/不适合的患者中，低强度的去甲基化剂（HMAs）和 venetoclax 治疗现在是新的护理标准。包含克拉屈滨、低剂量阿糖胞苷和其他靶向治疗（FLT3 和 IDH 抑制剂）的更好的低强度方案正在出现。维持治疗现在在 AML 的治疗中具有明确的作用，具有潜在治疗益处的口服 HMAs 也可用于治疗。总之，AML 治疗正在迅速发展，随着新型药物和策略被纳入传统 AML 化疗，所有 AML 亚组的治疗结果都在改善。
