Comment on Leleu et al , page 1968 , and Richardson et al , page 1961 “ IM iD ” eally treating multiple myeloma

cultural, and socioeconomic settings. Fortunately, additional advances are here, and more are on the way. Again, based on initial data from China, ATO has been established as a very effective treatment of relapsed APL and is the most active single agent for treatment of APL. In a randomized phase 3 trial by the North American Leukemia Intergroup, we demonstrated the effectiveness of ATO as initial consolidation therapy for patients in first remission; all recognized prognostic factors for disease-free survival were negated by the addition of ATO. Phase 2 studies have shown similar outcomes with incorporation of ATO into frontline therapy as consolidation and/or induction, with further decreases in chemotherapy exposure. Gore et al used ATRA plus daunorubicin induction followed by a single course of consolidation with cytarabine, daunorubicin, and ATO, and Ravandi et al developed a treatment regimen with no traditional chemotherapy. Mathews et al and Ghavamzadeh et al described promising results using single-agent ATO. At the December 2012 annual meeting of the American Society of Hematology, LoCoco and colleagues presented results of a randomized phase 3 trial that compared ATRA plus ATO with ATRA plus idarubicin in lowand intermediate-risk patients. At the same meeting Zhu et al reported results of the Chinese APL Cooperative Group randomized phase 3 trial that compared a new oral arsenic preparation with the current intravenous ATO as induction therapy for patients with untreated APL. Both trials were designed as noninferiority studies and both met endpoints with excellent outcomes, including response, disease-free survival, survival, and tolerance. While we await full peer-reviewed publications of these studies, both highlight continued progress. There remain important questions to be answered regarding APL. How do we avoid the 5% to 7% early deaths, primarily in patients presenting with high-risk disease (white blood cell counts . 10 3 10/L), that have persisted in multiple clinical trials? Perhaps the current US Intergroup trial for high-risk patients will show improvement with the early addition of gemtuzumab ozogamicin to ATRA and ATO. However, the phase 2 trial on which the study is based had an early death rate of 8%. How do we optimally manage the APL differentiation syndrome? How much, if any, chemotherapy is needed? If needed, then for what subgroup(s)? Is maintenance still needed in patients treated with ATO during induction and/or consolidation? Can we develop an arsenic preparation that maintains the current efficacy but can be delivered more conveniently to patients and with a high degree of compliance? Can we successfully disseminate current and future advances to colleagues in both developed and developing countries? The present is very good for our patients with APL, and the future is even brighter. Let us hope that we will all have the wisdom to recognize progress, the open minds to embrace it, and the commitment of Rego and colleagues needed for implementation. Conflict-of-interest disclosure: Dr Powell has served on an advisory board for Teva Pharmaceuticals. n