The Leukemia & Lymphoma Society, Rye Brook, NY, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Med. 2020 Dec;26(12):1852-1858. doi: 10.1038/s41591-020-1089-8. Epub 2020 Oct 26.
Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome. AML originates from a dominant mutation, then acquires collaborative transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Currently, AML treatment is initiated rapidly, precluding the ability to consider the mutational profile of a patient's leukemia for treatment decisions. Untreated patients with AML ≥ 60 years were prospectively enrolled on the ongoing Beat AML trial (ClinicalTrials.gov NCT03013998 ), which aims to provide cytogenetic and mutational data within 7 days (d) from sample receipt and before treatment selection, followed by treatment assignment to a sub-study based on the dominant clone. A total of 487 patients with suspected AML were enrolled; 395 were eligible. Median age was 72 years (range 60-92 years; 38% ≥75 years); 374 patients (94.7%) had genetic and cytogenetic analysis completed within 7 d and were centrally assigned to a Beat AML sub-study; 224 (56.7%) were enrolled on a Beat AML sub-study. The remaining 171 patients elected standard of care (SOC) (103), investigational therapy (28) or palliative care (40); 9 died before treatment assignment. Demographic, laboratory and molecular characteristics were not significantly different between patients on the Beat AML sub-studies and those receiving SOC (induction with cytarabine + daunorubicin (7 + 3 or equivalent) or hypomethylation agent). Thirty-day mortality was less frequent and overall survival was significantly longer for patients enrolled on the Beat AML sub-studies versus those who elected SOC. A precision medicine therapy strategy in AML is feasible within 7 d, allowing patients and physicians to rapidly incorporate genomic data into treatment decisions without increasing early death or adversely impacting overall survival.
急性髓细胞白血病（AML）是最常见的确诊白血病。在老年人中，AML 预后不良。AML 起源于优势突变，然后获得协同转化突变，导致髓系转化和临床/生物学异质性。目前，AML 的治疗迅速启动，无法在治疗决策时考虑患者白血病的突变谱。未接受治疗的 AML 患者年龄≥60 岁，前瞻性入组正在进行的 Beat AML 试验（ClinicalTrials.gov NCT03013998），该试验旨在在样本接收后 7 天内（d）内提供细胞遗传学和突变数据，然后在治疗选择之前，根据优势克隆将患者分配到亚研究中。共入组 487 例疑似 AML 患者；395 例符合条件。中位年龄为 72 岁（范围 60-92 岁；38%≥75 岁）；374 例（94.7%）在 7d 内完成了遗传和细胞遗传学分析，并在中心分配到 Beat AML 亚研究中；224 例（56.7%）入组了 Beat AML 亚研究。其余 171 例患者选择标准治疗（SOC）（103 例）、研究性治疗（28 例）或姑息治疗（40 例）；9 例在治疗分配前死亡。接受 Beat AML 亚研究和 SOC 的患者之间的人口统计学、实验室和分子特征没有显著差异（阿糖胞苷+柔红霉素[7+3 或等效]或低甲基化剂诱导治疗）。与选择 SOC 的患者相比，入组 Beat AML 亚研究的患者 30 天死亡率较低，总生存率显著延长。AML 中的精准医学治疗策略在 7d 内是可行的，允许患者和医生在不增加早期死亡或对总生存率产生不利影响的情况下，迅速将基因组数据纳入治疗决策。
