Arsenic Consolidation Allows Anthracycline Dose Reduction for Pediatric Patients with Acute Promyelocytic Leukemia: Report from the COG Phase III Historical Controlled trial AAML0631
APL0406 demonstrated that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) were not inferior in adults with acute promyelocytic leukemia (APL). This study reduced anthracyclines by 40% (to decrease risk of cardiotoxicity) and incorporated ATO in treatment for pediatric APL. The aim of this study was to demonstrate safety and tolerability of ATO in consolidation in pediatric patients and maintain same outcomes.
Nonrandomized, multicentre, phase III trial compared to historical data: AIDA 0493: 2-22 years old, de novo APL [t(15:17) confirmed by PML-RAR⍺ PCR]. The treatment protocol similar to AIDA 0493 except ATO 0.15mg/kg/d added to consolidation and cumulative daunorubicin equivalent reduction to 335mg/m2 for standard risk and 385mg/m2 for high-risk instead of 600mg/m2. Designed to detect an 11% decrease in EFS for SR patients.
Patients were enrolled from March 2009 - November 2012, 101 patients were evaluated. 3-year OS was 94% (SR 98%, HR 86%), 3-year EFS was 91% (SR 95%, HR 83%). AAML0631 was non-inferior to previous study. Events in this trial included 3 relapses, 2 second malignancies, and 7 deaths. Cardiac toxicities during ATO: 16% new grade 1 QTc prolongation, 12% grade 2 QTc prolongation, 1 patient grade 3 QTC prolongation, 1 patient grade 1 ventricular arrhythmia, 1 patient left ventricular dysfunction. Off therapy 1 patient grade 1 QTc prolongation, 1 patient grade 2 ventricular arrhythmia. There were no cardiac deaths and minimal liver toxicity.
Historical comparison with AIDA 0493 which enrolled patients between 1993-2000 and only descriptively described HR patients in this study.