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

• Type of Material: Article
• Authors: Amy Burd, Leukemia & Lymphoma Soc; Ross L Levine, Memorial Sloan Kettering Cancer Center; Amy S Ruppert, Ohio State University; Alice S Mims, Ohio State University; Uma Borate, Oregon Health & Science University; Eytan M Stein, Memorial Sloan Kettering Cancer Center; Prapti Patel, University of Texas Southwestern Medical Center; Maria R Baer, University of Maryland; Wendy Stock, University of Chicago; Michael Deininger, University of Utah; William Blum, Emory University; Gary Schiller, University of California Los Angeles; Rebecca Olin, University of California San Francisco; Mark Litzow, Mayo Clinic; James Foran, Mayo Clinic; Tara L Lin, University of Kansas; Brian Ball, Mem Sloan Kettering Cancer Center; Michael Boyiadzis, University of Pittsburgh; Elie Traer, Oregon Health & Science University; Olatoyosi Odenike, University of Chicago; Martha Arellano, Emory University; Alison Walker, Ohio State University; Vu H Duong, University of Maryland; Tibor Kovacsovics, University of Utah; Robert Collins, University of Texas Southwestern Medical Center; Abigail B Shoben, Ohio State University; Nyla A Heerema, Ohio State University; Matthew C Foster, University of North Carolina; Jo-Anne Vergilio, Foundation Medicine; Tim Brennan, Foundation Medicine; Christine Vietz, Foundation Medicine; Eric Severson, Foundation Medicine; Molly Miller, Ohio State University; Leonrad Rosenberg, The Leukemia & Lymphoma Society; Sonja Marcus, The Leukemia & Lymphoma Society; Ashley Yocum, The Leukemia & Lymphoma Society; Timothy Chen, Ohio State University; Mona Stefanos, Ohio State University; Brian Druker, Oregon Health & Science University; John C Byrd, Ohio State University
• Language: English
• Date: 2020-10-26
• Publisher: NATURE RESEARCH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41591-020-1089-8
• Title of Journal or Parent Work: NATURE MEDICINE
• Volume: 26
• Issue: 12
• Start Page: 1852
• End Page: 1858
• Keywords: THERAPY; Science & Technology; PHASE-III; Life Sciences & Biomedicine; OLDER PATIENTS; CHEMOTHERAPY; PROTEIN; Medicine, Research & Experimental; ELDERLY-PATIENTS; Biochemistry & Molecular Biology; CANCER; Research & Experimental Medicine; MUTATIONS; Cell Biology; DECITABINE; SUPPORTIVE CARE

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.