Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups

Marlise R. Luskin, Ju Whei Lee, Hugo F. Fernandez, Omar Abdel-Wahab, John M. Bennett, Rhett P. Ketterling, Hillard M. Lazarus, Ross L. Levine, Mark R. Litzow, Elisabeth M. Paietta, Jay P. Patel, Janis Racevskis, Jacob M. Rowe, Martin S. Tallman, Zhuoxin Sun, Selina M. Luger

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1551-1558
Number of pages8
JournalBlood
Volume127
Issue number12
DOIs
StatePublished - Mar 24 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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