臨床試驗揭示急性髓系白血病治療中基因組分析對於精準醫療的可行性與效率
作者：
小柯機器人發布時間：2020/10/28 15:12:33
2020年10月26日，美國俄亥俄州立大學John C. Byrd研究小組在《自然—醫學》雜誌發表論文，揭示了急性髓系白血病治療中基因組分析對於精準醫療的可行性與效率。
研究人員前瞻性將地未接受治療的≥60歲的急性髓細胞性白血病（AML）患者進入Beat AML試驗（ClinicalTrials.gov NCT03013998），該試驗的的目的是在樣本接收後至選擇治療前的7天內提供細胞遺傳學和突變數據，然後分配至基於優勢克隆的子項治療研究。共有487名疑似AML患者入組。395位符合資格。中位年齡為72歲（60-92歲； 38％≥75歲）。374例患者（94.7％）在7天內完成了遺傳和細胞遺傳學分析，併集中分配給Beat AML子項研究。
224名（56.7％）參加了Beat AML子項研究。將剩餘的171例患者選為標準護理（SOC）（103）、研究性治療（28）或姑息治療（40）；9名患者在接受治療前死亡。在Beat AML子項研究的患者和接受SOC（用阿糖胞苷+柔紅黴素（7+3或同等水平）或次甲基化劑誘導）的患者之間，人口統計學、實驗室和分子特徵無明顯差異。與選擇SOC的患者相比，Beat AML子項研究的患者30天死亡率較低，總生存期明顯更長。因此，AML的精確藥物治療策略在7天之內是可行的，使患者和醫生可以將基因組數據快速納入治療決策，而不會增加早期死亡或對總體生存率產生不利影響。
據了解，AML是最常見的診斷出的白血病。在老年人中，AML會帶來不利的結果。AML源自顯性突變，然後獲得協同轉化突變，最終導致髓樣轉化和臨床/生物學異質性。目前，AML治療會被迅速啟動，並不考慮患者白血病突變情況。
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