Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia. Analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group

In standard risk acute promyelocytic leukemia, recent results have shown that ATRA + Arsenic trioxide combinations were at least as effective as classical ATRA + anthracycline based chemotherapy while being less myelosuppressive. However, the role of frontline arsenic trioxide is less clear in higher risk acute promyelocytic leukemia, and access to arsenic remains limited for frontline treatment of standard risk acute promyelocytic leukemia in many countries. In this randomized trial, we compared for consolidation treatment (after ATRA-Chemotherapy induction treatment) arsenic, ATRA and the classical AraC in standard risk acute promyelocytic leukemia, and evaluated the addition of arsenic during consolidation in higher risk APL. Newly diagnosed acute promyelocytic leukemia patients with white blood cells < 10 G/L, after an induction treatment consisting of ATRA plus Idarubicin-AraC, received consolidation chemotherapy with Idarubicin and AraC, arsenic or ATRA. Patients with white blood cells >10G received consolidation chemotherapy with arsenic or without arsenic.795 acute promyelocytic leukemia patients were enrolled in this trial. In Standard risk APL (n= 581), 5-year EFS from randomization was 88.7%, 95.7% and 85.4% in the AraC, arsenic and ATRA consolidation groups, respectively (p=0.0067) and 5 year cumulative incidence of relapse (CIR) was 5.5%, 0% and 8.2%. (p=0.001). In higher risk APL (n=214), 5-year EFS was 85.5% vs 92.1% (p=0.38) in the chemotherapy and chemotherapy+ arsenic groups, respectively and 5-year CIR of 4.6% and 3.5% (p= 0.99) in the chemotherapy and chemotherapy+ arsenic groups. Due to prolonged myelosuppression in the chemotherapy+ arsenic arm, an amendment excluded AraC during consolidation cycles in the chemotherapy+ arsenic group, resulting in no increase in relapse. Our results therefore advocate systematic introduction of arsenic in the first line treatment of acute promyelocytic leukemia, but probably not concomitantly with intensive chemotherapy, a situation where we found myelosuppression to be significant. (ClinicalTrials.gov Identifier: NCT00378365).