• Andrew H Wei, Hartmut Döhner, Christopher Pocock, Pau Montesinos, Boris Afanasyev, Hervé Dombret, Farhad Ravandi, Hamid Sayar, Jun-Ho Jang, Kimmo Porkka, Dominik Selleslag, Irwindeep Sandhu, Mehmet Turgut, Valentina Giai, Yishai Ofran, Kizil Çakar Merih M From the Department of Clinical Haematology, Alfred Hospital, and the Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Austral, Aida Botelho de Sousa, Justyna Rybka, Chiara Frairia, Lorenza Borin, Germana Beltrami, Jaroslav Čermák, Gert J Ossenkoppele, Ignazia La Torre, Barry Skikne, Keshava Kumar, Qian Dong, C L Beach, Gail J Roboz, and QUAZAR AML-001 Trial Investigators.
• From the Department of Clinical Haematology, Alfred Hospital, and the Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia (A.H.W.); the Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany (H. Döhner); Kent and Canterbury Hospital, Canterbury, United Kingdom (C.P.); Centro de Investigación Biomédica en Red de Cáncer, Instituto Carlos III, Madrid, and Hospital Universitari i Politècnic La Fe, Valencia - both in Spain (P.M.); Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia (B.A.); the Department of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, and Institut de Recherche Saint-Louis, Université de Paris, Paris (H. Dombret); the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (F.R.); Indiana University Cancer Center, Indianapolis (H.S.); Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (J.H.J.); Hospital District of Helsinki and Uusimaa (HUS) Comprehensive Cancer Center, Hematology Research Unit Helsinki and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki, Helsinki (K.P.); AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium (D.S.); University of Alberta Hospital, Edmonton, Canada (I.S.); Ondokuz Mayis University, Samsun (M.T.), and Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara (M.K.C.) - both in Turkey; Antonio e Biagio e Cesare Arrigo Hospital, Alessandria (V.G.), Città della Salute e della Scienza, Turin (C.F.), Ospedale San Gerardo Monza, Monza (L.B.), and Ospedale Policlinico San Martino, Genoa (G.B.) - all in Italy; Rambam Medical Center and Faculty of Medicine Technion, Haifa, Israel (Y.O.); Hospital dos Capuchos, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal (A.B.S.); Wroclaw Medical University, Wroclaw, Poland (J.R.); Ústav Hematologie a Krevní Transfuze, Prague, Czech Republic (J.C.); Amsterdam University Medical Center, Location VUMC (Vrije Universiteit Medical Center), Amsterdam (G.J.O.); Celgene (Bristol Myers Squibb), Boudry, Switzerland (I.L.T.); Bristol Myers Squibb, Princeton, NJ (B.S., K.K., Q.D., C.L.B.); University of Kansas Medical Center, Kansas City (B.S.); and Weill Cornell Medicine and New York Presbyterian Hospital, New York (G.J.R.).
• N. Engl. J. Med. 2020 Dec 24; 383 (26): 2526-2537.

BackgroundAlthough induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.MethodsWe conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life.ResultsA total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment.ConclusionsCC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment. (Supported by Celgene; QUAZAR AML-001 ClinicalTrials.gov number, NCT01757535.).Copyright © 2020 Massachusetts Medical Society.

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