临床试验揭示急性髓系白血病治疗中基因组分析对于精准医疗的可行性与效率-小柯机器人-科学网

临床试验揭示急性髓系白血病治疗中基因组分析对于精准医疗的可行性与效率

2020-10-28 15:12

2020年10月26日，美国俄亥俄州立大学John C. Byrd研究小组在《自然—医学》杂志发表论文，揭示了急性髓系白血病治疗中基因组分析对于精准医疗的可行性与效率。

研究人员前瞻性将地未接受治疗的≥60岁的急性髓细胞性白血病（AML）患者进入Beat AML试验（ClinicalTrials.gov NCT03013998），该试验的的目的是在样本接收后至选择治疗前的7天内提供细胞遗传学和突变数据，然后分配至基于优势克隆的子项治疗研究。共有487名疑似AML患者入组。395位符合资格。中位年龄为72岁（60-92岁； 38％≥75岁）。374例患者（94.7％）在7天内完成了遗传和细胞遗传学分析，并集中分配给Beat AML子项研究。

224名（56.7％）参加了Beat AML子项研究。将剩余的171例患者选为标准护理（SOC）（103）、研究性治疗（28）或姑息治疗（40）；9名患者在接受治疗前死亡。在Beat AML子项研究的患者和接受SOC（用阿糖胞苷+柔红霉素（7+3或同等水平）或次甲基化剂诱导）的患者之间，人口统计学、实验室和分子特征无明显差异。与选择SOC的患者相比，Beat AML子项研究的患者30天死亡率较低，总生存期明显更长。因此，AML的精确药物治疗策略在7天之内是可行的，使患者和医生可以将基因组数据快速纳入治疗决策，而不会增加早期死亡或对总体生存率产生不利影响。

据了解，AML是最常见的诊断出的白血病。在老年人中，AML会带来不利的结果。AML源自显性突变，然后获得协同转化突变，最终导致髓样转化和临床/生物学异质性。目前，AML治疗会被迅速启动，并不考虑患者白血病突变情况。

附：英文原文

Title: Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial

Author: Amy Burd, Ross L. Levine, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Prapti Patel, Maria R. Baer, Wendy Stock, Michael Deininger, William Blum, Gary Schiller, Rebecca Olin, Mark Litzow, James Foran, Tara L. Lin, Brian Ball, Michael Boyiadzis, Elie Traer, Olatoyosi Odenike, Martha Arellano, Alison Walker, Vu. H. Duong, Tibor Kovacsovics, Robert Collins, Abigail B. Shoben, Nyla A. Heerema, Matthew C. Foster, Jo-Anne Vergilio, Tim Brennan, Christine Vietz, Eric Severson, Molly Miller, Leonard Rosenberg, Sonja Marcus, Ashley Yocum, Timothy Chen, Mona Stefanos, Brian Druker, John C. Byrd

Issue&Volume: 2020-10-26

Abstract: Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome1,2. 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. Preliminary results from the Beat AML umbrella trial demonstrates the feasibility and efficacy of applying prospective genomic profiling for matching newly diagnosed patients with AML with targeted therapies.

DOI: 10.1038/s41591-020-1089-8

Source: https://www.nature.com/articles/s41591-020-1089-8

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex

本期文章：《自然—医学》：Online/在线发表

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