Effect of consolidation with arsenic trioxide (As 2 O 3 ) on event-free survival (EFS) and overall survival (OS) among patients with newly diagnosed acute promyelocytic leukemia (APL): North American Intergroup Protocol C9710

2 Background: This randomized phase III study was designed to evaluate the benefit and toxicity of two 25-day courses of As 2 O 3 as first post-remission therapy for newly diagnosed patients with APL. Methods: Adult patients were randomized to receive 2 courses of As 2 O 3 (0.15 mg/kg/d for 5d each wk for 5 wk) as a first consolidation if they achieved remission (CR or PR) after induction with oral tretinoin (ATRA; 45 mg/m 2 /d), daunorubicin (50 mg/m 2 IV × 4d), and cytarabine (200 mg/m 2 CIV × 7d); by study design, all but 2 children were assigned to the non-As 2 O 3 arm. Subsequent consolidation on both arms included 2 courses of ATRA (45 mg/m 2 × 7d) + daunorubicin (50 mg/m 2 × 3d; 2d for age < 15 yr). CR patients were then randomized to 1 yr of ATRA maintenance (7d repeated every other wk) with or without 6- mercaptopurine (daily) + methotrexate (weekly). Results: 518 adults (15–79 yr) and 64 children (<15 yr; 11%) with untreated APL were enrolled by 5 cooperative groups (CALGB, ECOG, SWOG, COG, NCIC-CTG). Eligibility required demonstration of PML-RARA in one of 3 central labs; 37 adults and 7 children were ineligible and not included in the analyses. Patient characteristics and toxicity data have been reported (ASH 2006; Blood 108:171a). Median follow up is now 29 mos. Overall CR rate for adults was 89% and did not differ by treatment arm; CR rate for children was 89%. There were 41 deaths (8%) within 60 days. EFS, the primary endpoint, was 77% at 3 yrs on the As 2 O 3 arm (median, not reached) compared to 59% at 3 yrs on the standard arm (median, 63 mos; p=0.0013). Overall, 84% of adults were alive at last follow up. OS was 86% at 3 yrs on the As 2 O 3 arm compared to 77% at 3 yrs on the standard arm (medians not reached; p=0.029); EFS and OS for pediatric patients did not differ statistically from the adult arm without As 2 O 3 . Among 452 CR pts, there have been only 71 post-CR events (16%) so disease- free survival has not yet been analyzed by treatment arm. Conclusion: The addition of 2 courses of As 2 O 3 consolidation following remission induction significantly improves EFS and OS in adults with APL. No significant financial relationships to disclose.