• Courtney D DiNardo, Brian A Jonas, Vinod Pullarkat, Michael J Thirman, Jacqueline S Garcia, Andrew H Wei, Marina Konopleva, Hartmut Döhner, Anthony Letai, Pierre Fenaux, Elizabeth Koller, Violaine Havelange, Brian Leber, Jordi Esteve, Jianxiang Wang, Vlatko Pejsa, Roman Hájek, Kimmo Porkka, Árpád Illés, David Lavie, Roberto M Lemoli, Kazuhito Yamamoto, Sung-Soo Yoon, Jun-Ho Jang, Su-Peng Yeh, Mehmet Turgut, Wan-Jen Hong, Ying Zhou, Jalaja Potluri, and Keith W Pratz.
• From the Department of Leukemia, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (C.D.D., M.K.); the Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento (B.A.J.), the Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte (V. Pullarkat), and Genentech, South San Francisco (W.-J.H.) - all in California; the Section of Hematology and Oncology, Department of Medicine, University of Chicago Medicine, Chicago (M.J.T.), and AbbVie, North Chicago (Y.Z., J.P.) - both in Illinois; the Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston (J.S.G., A.L.); the Australian Centre for Blood Diseases, Alfred Hospital and Monash University, Melbourne, VIC (A.H.W.); the Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany (H.D.); Hôpital St. Louis, Assistance Publique-Hôpitaux de Paris and Université de Paris, Paris (P.F.); the Third Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna (E.K.); the Department of Hematology, Cliniques Universitaires Saint-Luc, Brussels (V.H.); the Department of Medicine, McMaster University, Hamilton, ON, Canada (B.L.); the Department of Hematology, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Barcelona (J.E.); the Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China (J.W.); the Department of Hematology, University Hospital Dubrava, University of Zagreb School of Medicine, Zagreb, Croatia (V. Pejsa); the Department of Clinic Subjects, University Hospital Ostrava-Poruba, Ostrava, Czech Republic (R.H.); Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki (K.P.); the Faculty of Medicine, Department of Hematology, University of Debrecen, Debrecen, Hungary (A.I.); Hadassah Medical Center, Jerusalem (D.L.); the Clinic of Hematology, Department of Internal Medicine, University of Genoa, and San Martino Hospital IRCCS - both in Genoa, Italy (R.M.L.); the Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan (K.Y.); the Department of Internal Medicine, Seoul National University College of Medicine (S.-S.Y.), and the Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine (J.-H.J.) - both in Seoul, South Korea; the Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan (S.-P.Y.); the Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ondokuz Mayıs University, Samsun, Turkey (M.T.); and Abramson Cancer Center, University of Pennsylvania, Philadelphia (K.W.P.).
• N. Engl. J. Med. 2020 Aug 13; 383 (7): 617629617-629.

BackgroundOlder patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study.MethodsWe randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival.ResultsThe intention-to-treat population included 431 patients (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine-venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine-venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively.ConclusionsIn previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.).Copyright © 2020 Massachusetts Medical Society.

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