학술논문
Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial
Document Type
article
Author
Burd, Amy; Levine, Ross L; Ruppert, Amy S; Mims, Alice S; Borate, Uma; Stein, Eytan M; Patel, Prapti; Baer, Maria R; Stock, Wendy; Deininger, Michael; Blum, William; Schiller, Gary; Olin, Rebecca; Litzow, Mark; Foran, James; Lin, Tara L; Ball, Brian; Boyiadzis, Michael; Traer, Elie; Odenike, Olatoyosi; Arellano, Martha; Walker, Alison; Duong, Vu H; Kovacsovics, Tibor; Collins, Robert; Shoben, Abigail B; Heerema, Nyla A; Foster, Matthew C; Vergilio, Jo-Anne; Brennan, Tim; Vietz, Christine; Severson, Eric; Miller, Molly; Rosenberg, Leonard; Marcus, Sonja; Yocum, Ashley; Chen, Timothy; Stefanos, Mona; Druker, Brian; Byrd, John C
Source
Nature Medicine. 26(12)
Subject
Language
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.