Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia

• Published in: Leukemia Vol. 30; no. 3; pp. 555 - 561
• Main Authors: Müller-Tidow, C, Tschanter, P, Röllig, C, Thiede, C, Koschmieder, A, Stelljes, M, Koschmieder, S, Dugas, M, Gerss, J, Butterfaß-Bahloul, T, Wagner, R, Eveslage, M, Thiem, U, Krause, S W, Kaiser, U, Kunzmann, V, Steffen, B, Noppeney, R, Herr, W, Baldus, C D, Schmitz, N, Götze, K, Reichle, A, Kaufmann, M, Neubauer, A, Schäfer-Eckart, K, Hänel, M, Peceny, R, Frickhofen, N, Kiehl, M, Giagounidis, A, Görner, M, Repp, R, Link, H, Kiani, A, Naumann, R, Brümmendorf, T H, Serve, H, Ehninger, G, Berdel, W E, Krug, U
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 13/31; 38/77; 692/308/2779; 692/699/1541/1990/283/1897; Acute myeloid leukemia; Aged; Aged patients; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Azacitidine - therapeutic use; Cancer Research; Chemotherapy; Critical Care Medicine; Cytarabine - therapeutic use; Cytogenetic Analysis; Cytogenetics; Daunorubicin - therapeutic use; DNA methylation; DNA methyltransferase; Female; Health aspects; Hematology; Humans; Induction Chemotherapy - methods; Intensive; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Male; Medicine; Medicine & Public Health; Methylation; Middle Aged; Oncology; original-article; Remission Induction; Survival; Survival Analysis; Toxicity; Germany
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2015.306

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics ( P =0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, ( P =0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P =0.76). Median EFS was 6 months in both arms ( P =0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B ( P =0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.