Comparison of epigenetic versus standard induction chemotherapy for newly diagnosed acute myeloid leukemia patients ≥60 years old

Am J Hematol. 2015 Jul;90(7):639-46. doi: 10.1002/ajh.24016.

Abstract

Older patients with acute myeloid leukemia (AML) have poor outcomes with standard induction chemotherapy. We retrospectively reviewed our institute's experience with epigenetic (Epi) versus cytarabine- and anthracycline-based intensive chemotherapy (IC) as induction in newly diagnosed AML patients aged 60 years and older. One hundred sixty-seven patients (n = 84, IC; n = 83, Epi) were assessed; 69 patients received decitabine and 14 azacitidine. Baseline characteristics between the IC and Epi patient cohorts were not statistically different except for age, initial white blood cell count, and comorbidity index. Overall response rate (ORR, 50% vs. 28%, respectively, P < 0.01) and complete response rate (CRR, 43% vs. 20%, respectively, P < 0.01) were superior following IC vs. Epi. Although univariate analysis demonstrated longer overall survival after IC (10.7 vs. 9.1 months, P = 0.012), multivariate analysis showed no independent impact of induction treatment. Treatment-related mortality was not statistically different in the two groups. Outcomes of patients with secondary, poor cytogenetic risk, FLT-3 mutated AML, or relapsed/refractory disease after IC or Epi were not significantly different. Outcomes of patients receiving IC versus a 10-day decitabine regimen (n = 63) also were not significantly different. Our results suggest that IC and Epi therapy are clinically equivalent approaches for upfront treatment of older patients with AML and that other factors (feasibility, toxicity, cost, etc.) should drive treatment decisions. Prospective randomized trials to determine the optimal induction approach for specific patient subsets are needed.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / therapeutic use
  • Cytarabine / therapeutic use*
  • Decitabine
  • Epigenesis, Genetic
  • Female
  • Humans
  • Induction Chemotherapy / methods*
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Leukocyte Count
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Remission Induction
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Antimetabolites, Antineoplastic
  • Nuclear Proteins
  • Cytarabine
  • Nucleophosmin
  • Decitabine
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Azacitidine