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Which Anthracycline for AML Induction Therapy?
Standard induction therapy for acute myeloid leukemia (AML) includes a 7-day infusion of cytarabine plus 3 days of daunorubicin or idarubicin.
Now, Korean investigators have conducted a randomized, unblinded, phase III study of 299 newly diagnosed AML patients (ages, 15–65 years) to compare the use of cytarabine (200 mg/m2) on days 1 through 7 plus either high-dose daunorubicin (90 mg/m2) or standard-dose idarubicin (12 mg/m2) on days 1 through 3. Patients achieving complete remission (CR) could proceed to consolidation chemotherapy or stem-cell transplantation in first CR.
CR rates were similar with daunorubicin or idarubicin (66.7% and 71.1%, respectively), as was 4-year overall survival (OS; 54.7% and 51.1%), although the treatment arms were unbalanced, in that a higher number of daunorubicin recipients had secondary AML and both good- and poor-risk cytogenetics. Patients with the poor-risk FLT3-ITD mutation had improved median OS with daunorubicin (not reached vs. 15.5 months; P=0.03). Adverse events were similar, aside from slower platelet recovery with idarubicin.
Comment
Clinical AML trials of anthracyclines and dose-intensity have generally shown outcomes with idarubicin (12 mg/m2) or daunorubicin (60–90 mg/m2) induction to be equivalent. They have also demonstrated a benefit for high-dose daunorubicin in FLT3-ITD positive AML, as observed in the current trial. For this poor-risk subset, the FLT3 inhibitor midostaurin in combination with AD induction was shown to provide significant benefit (NEJM JW Oncol Hematol Sep 2017 and N Engl J Med 2017 377:454) and was approved in the U.S. for this indication. As AML molecular profiling is further refined and incorporated into treatment planning, either for induction or to guide the use of allogeneic stem-cell transplantation in first CR, continued progress in AML is anticipated.
Citation(s)
Author:
Lee JH et al.
Title:
Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia.
Source:
J Clin Oncol
2017
Aug
20; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Michael E. Williams, MD, ScM