A randomized trial of anthracycline dose intensification during induction of younger patients with acute myeloid leukemia: Results of Eastern Cooperative Oncology Group study E1900

Abstract

7003 Background: In younger adults with newly diagnosed acute myeloid leukemia (AML), anthracycline dose intensification during induction may improve complete remission (CR) rates; however, an improvement in overall survival (OS) in a randomized trial has not been demonstrated. This unresolved issue led the ECOG to compare standard dose (SDD) to high-dose daunorubicin (HDD) in induction. Methods: Adult patients with previously untreated AML were randomized to receive either SDD (45 mg/m2/d) or HDD (90 mg/m2/d) each for 3days combined with standard-dose cytarabine (100 mg/m2/d) for 7 days by continuous intravenous infusion. Those achieving a CR were allocated to allogeneic hematopoietic stem cell transplantation (HSCT) or high-dose cytarabine (with or without a single dose of gemtuzumab ozogamicin) prior to autologous HSCT. Intravenous busulfan and cyclophosphamide was the preparative regimen for both allogeneic and autologous HSCT. The primary end point of this study was OS from the time of induction randomization. Results: 633 patients, age 18 to 60 (median 48) years, were entered in this study. There were no differences in patient demographics or disease characteristics between the two groups at presentation. In an intention-to-treat analysis, HDD resulted in a significantly higher CR rate (63.3% vs. 47.7%, p = 0.0003) than SDD. Induction deaths were similar between the two groups (5.4 vs. 5.0%, p = ns). 334 (52.8%) patients entered the consolidation phase. 57.4% of HDD and 48.1% of the SDD patients, received consolidation therapy on study, and 28.7% and 23.1% proceeded to HSCT respectively. Median OS was superior for the HDD (23.7 months) over the SDD (15.1 months) group (p = 0.005). In subgroup analysis, patients with favorable or intermediate-risk cytogenetics or age <55 years benefited from the HDD. Conclusions: We demonstrate for the first time in a prospective randomized trial that intensifying induction therapy through a higher daily anthracycline dose, in the setting of identical intensive consolidation therapy, results in a higher CR rate as well as prolonged OS. In younger AML patients a higher dose of anthracycline in induction should be considered the new standard of care. No significant financial relationships to disclose.