| Autor: |
Döhner H; Ulm University Hospital, Ulm, Germany. hartmut.doehner@uniklinik-ulm.de., Dolnik A; Ulm University Hospital, Ulm, Germany., Tang L; Celgene Corporation, Summit, NJ, United States., Seymour JF; Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Melbourne, and University of Melbourne, Parkville, Australia., Minden MD; University of Toronto, Toronto, ON, Canada., Stone RM; Dana-Farber Cancer Institute, Boston, MA, United States., Del Castillo TB; Hospital Central de Asturias, Oviedo, Spain., Al-Ali HK; Universitätsklinikum Halle (Saale), Halle, Germany., Santini V; AOU Careggi, University of Florence, Florence, Italy., Vyas P; University of Oxford, Oxford, United Kingdom., Beach CL; Celgene Corporation, Summit, NJ, United States., MacBeth KJ; Celgene Corporation, Summit, NJ, United States., Skikne BS; Celgene Corporation, Summit, NJ, United States., Songer S; Celgene Corporation, Summit, NJ, United States., Tu N; Celgene Corporation, Summit, NJ, United States., Bullinger L; Ulm University Hospital, Ulm, Germany.; Charité University Medicine, Berlin, Germany., Dombret H; Hôpital Saint Louis, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France. |
| Abstrakt: |
Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m 2 /day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≥10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. There was a significant OS improvement with azacitidine vs CCR for patients with European LeukemiaNet-defined Adverse karyotype (HR 0.71 [95%CI 0.51-0.99]; P = 0.046). Azacitidine-treated patients with -5/5q-, -7/7q-, or 17p abnormalities, or with monosomal or complex karyotypes, had a 31-46% reduced risk of death vs CCR. The most frequent gene mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and TP53 (21%). Compared with wild-type, OS was significantly reduced among CCR-treated patients with TP53 or NRAS mutations and azacitidine-treated patients with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older patients with AML with Adverse-risk cytogenetics, particularly those with chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The influence of gene mutations in azacitidine-treated patients warrants further study. |
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