Scientific programme

P06  Poster Session - May 4 - May 6
CURRENT TREATMENT OPTIONS - HYPOMETHYLATING AGENTS (AZACITIDINE, DECITABINE)

04-May-2017 08:00 17:00
 
 
Abstract: 048
AZACITIDINE PROLONGS OVERALL SURVIVAL IN OLDER PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) WITH POOR PROGNOSTIC KARYOTYPES

Background: Prognosis is dismal for older AML patients with unfavorable karyotypes. In the phase 3 AZA-AML-001 study, azacitidine prolonged overall survival (OS) by 3.2 months vs conventional care regimens (CCR) (P=0.0185) in older patients with AML and NCCN-defined Poor-risk cytogenetics (Döhner et al, Blood, 2014). We compared OS with azacitidine vs CCR in patient subgroups defined by specific cytogenetic abnormalities and by modified European LeukemiaNet (ELN)-defined cytogenetic-risk classifications (Döhner et al, Blood, 2010).

Methods: Patients aged ≥65 years with newly diagnosed AML (>30% blasts) and NCCN-defined Intermediate- or Poor-risk cytogenetics received azacitidine (75mg/m2/day x 7 days/28-day cycle) or CCR: intensive chemotherapy, low-dose cytarabine, or best-supportive-care only. Bone marrows were centrally reviewed by an independent cytogeneticist. OS was assessed for patients with ELN-defined Intermediate-I (normal karyotype), Intermediate-II (abnormalities not classified as favorable/adverse), and Adverse karyotypes; and for patients with frequent (≥10% of patients) cytogenetic abnormalities (-5/5q-, -7, -7/7q-, abnormal 17p) and monosomal or complex karyotypes.

Results: Cytogenetic data were available for 485/488 patients. Median OS was comparable between treatment arms in the Intermediate-I and Intermediate-II risk subgroups (Table). There was a significant 2.4-month median OS increase for azacitidine-treated patients with Adverse karyotype vs CCR (hazard ratio [HR] 0.71, 95%CI 0.51–0.99; P=0.046) (Figure), with 1-year survival of 29.1% vs 14.7%, respectively. Azacitidine was associated with longer median OS and higher 1-year survival vs CCR for all abnormality/karyotype subgroups (Table), with HRs ranging from 0.54–0.69. Patients with chromosome 7 abnormalities responded particularly well to azacitidine, with a 4.1-month improvement in OS vs CCR. Patients with complex karyotypes also had meaningful improvements in OS, with ~15% more azacitidine-treated patients alive at 1 year.

Conclusions: Median OS and 1-year survival in patients with ELN-defined Adverse karyotype treated with azacitidine were almost double those for CCR-treated patients. Azacitidine-treated patients with the frequent abnormalities assessed here or with monosomal or complex karyotypes had 31-46% reduced risk of death vs CCR, and 1-year survival was 11-22% greater with azacitidine. These data suggest azacitidine should be preferred treatment for older patients with AML and adverse karyotypes.



 
Co-authors
H. Döhner 1, P. Vyas 2, J.F. Seymour 3,4, V. Santini 5, R.M. Stone 6, M.D. Minden 7, H.K. Al-Ali 8, T. Bernal del Castillo 9, J. Morrill 10, S. Songer 11, J. Weaver 10, B.S. Skikne 11, C.L. Beach 11, H. Dombret 12
1Universitätsklinikum Ulm, Department of Internal Medicine III, Ulm, Germany
2University of Oxford, Department of Haematology, Oxford, United Kingdom
3Peter MacCallum Cancer Centre, Department of Haematology, Melbourne, Australia
4University of Melbourne, Department of Haematology, Parkville, Australia
5University of Florence, Division of Hematology, Florence, Italy
6Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, USA
7Princess Margaret Cancer Centre, Department of Medical Biophysics, Toronto, Canada
8University Hospital of Halle, Department of Hematology/Oncology, Halle, Germany
9Hospital Central de Asturias, Department of Hematology and Hemotherapy, Oviedo, Spain
10Celgene Corporation, Department of Biostatistics, Summit, USA
11Celgene Corporation, Department of Hematology/Oncology, Summit, USA
12Hôpital Saint Louis- Institut Universitaire d’Hématologie- University Paris Diderot, Department of Hematology, Paris, France