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Comparative Study
. 2015 Jul;90(7):639-46.
doi: 10.1002/ajh.24016.

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

Neha Gupta  1 , Austin Miller  2 , Shipra Gandhi  1 , Laurie A Ford  3 , Carlos E Vigil  3 , Elizabeth A Griffiths  3 , James E Thompson  3 , Meir Wetzler  3 , Eunice S Wang  3
Affiliations
Comparative Study

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

Neha Gupta et al. Am J Hematol. 2015 Jul.

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.

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Conflict of interest statement

Conflict of interest

The authors report no potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Outcomes of older AML patients treated with different induction strategies. (A) Overall survival of older AML patients following induction with intensive chemotherapy (IC) or epigenetic (Epi) therapy. Median survival of the IC group was 10.7 months as compared with 9.1 months in the Epi-treated patients (P = 0.012). (B) Leukemia-free survival of patients following IC or epigenetic therapy. Median survival of IC group was 29.2 months as compared with 9.2 months (P = 0.090). (C) Overall survival of older AML patients following induction with IC or 10 days of decitabine (Dec10). Median survival of the IC group was 10.7 months as compared with 8.0 months in the Dec10-treated patients (P = 0.026). (D) Leukemia-free survival of patients following induction with IC or Dec10. Median survival time of IC group was 29.2 months as compared with 10.3 months following Dec10 treatment (P = 0.239). Epi (solid line), epigenetic therapy; IC (dotted line), intensive chemotherapy; median, median overall survival.
Figure 2.
Figure 2.
Impact of induction therapy on survival of subgroups of older AML patients. Overall survival of patients defined by (A) poor cytogenetics; (B) secondary AML; (C) presence of FLT-3 mutations; and (D) presence of NPM-1 mutations are shown. Epi (solid line), epigenetic therapy; IC (dotted line), intensive chemotherapy; median, median overall survival; NR, not reached.
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