TY - JOUR
T1 - Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups
AU - Luskin, Marlise R.
AU - Lee, Ju Whei
AU - Fernandez, Hugo F.
AU - Abdel-Wahab, Omar
AU - Bennett, John M.
AU - Ketterling, Rhett P.
AU - Lazarus, Hillard M.
AU - Levine, Ross L.
AU - Litzow, Mark R.
AU - Paietta, Elisabeth M.
AU - Patel, Jay P.
AU - Racevskis, Janis
AU - Rowe, Jacob M.
AU - Tallman, Martin S.
AU - Sun, Zhuoxin
AU - Luger, Selina M.
N1 - Funding Information:
Acknowledgments This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA180867, CA180791, CA180790, CA180583, and CA189859, the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. This study's content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute
Publisher Copyright:
© 2016 by The American Society of Hematology.
PY - 2016/3/24
Y1 - 2016/3/24
N2 - The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m2) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or a FLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m2), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P 5 .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66; P 5 .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51; P 5 .03 andHR, 0.68;P5.01, respectively). Patients with unfavorable cytogenetics wereshownto benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66; P 5 .04). Patients with FLT3-ITD (24%), DNMT3A (24%), and NPM1 (26%) mutant AML all benefited from HDdaunorubicin (HR, 0.61, P5.009; HR, 0.62, P5.02; and HR, 0.50, P5.002; respectively).HD benefit was seen in the subgroup of older patients (50-60 years) with the FLT3-ITD or NPM1 mutation. Additionally, the presence of an NPM1 mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction.
AB - The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m2) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or a FLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m2), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P 5 .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66; P 5 .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51; P 5 .03 andHR, 0.68;P5.01, respectively). Patients with unfavorable cytogenetics wereshownto benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66; P 5 .04). Patients with FLT3-ITD (24%), DNMT3A (24%), and NPM1 (26%) mutant AML all benefited from HDdaunorubicin (HR, 0.61, P5.009; HR, 0.62, P5.02; and HR, 0.50, P5.002; respectively).HD benefit was seen in the subgroup of older patients (50-60 years) with the FLT3-ITD or NPM1 mutation. Additionally, the presence of an NPM1 mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction.
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U2 - 10.1182/blood-2015-07-657403
DO - 10.1182/blood-2015-07-657403
M3 - Article
C2 - 26755712
AN - SCOPUS:84962304176
SN - 0006-4971
VL - 127
SP - 1551
EP - 1558
JO - Blood
JF - Blood
IS - 12
ER -