OVERALL SURVIVAL (OS) AND CLINICAL OUTCOMES IN OLDER PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) TREATED WITH AZACITIDINE (AZA) OR LOW-DOSE CYTARABINE (LDAC) IN THE AZA-AML-001 STUDY
Author(s): ,
John F. Seymour
Affiliations:
Peter MacCallum Cancer Centre,East Melbourne,Australia
,
Hartmut Döhner
Affiliations:
Universitätsklinikum Ulm,Ulm,Germany
,
Rajat Kumar
Affiliations:
Cancer Care Manitoba,Winnipeg,Canada
,
Richard M Stone
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Agnieszka Wierzbowska
Affiliations:
Medical University of Lodz,Lodz,Poland
,
Teresa Bernal del Castillo
Affiliations:
Hospital Central de Asturias,Oviedo,Spain
,
Jose Falantes
Affiliations:
Hospital Universitario Virgen del Rocio/Instituto de BioMedicinia de Sevilla,Sevilla,Spain
,
Jacques Delaunay
Affiliations:
CHU Nantes Hôtel Dieu,Nantes,France
,
Mitchell Sabloff
Affiliations:
University of Ottawa and Ottawa Hospital Research Institute,Ottawa,Canada
,
Maria Teresa Voso
Affiliations:
Universita’ Tor Vergata,Rome,Italy
,
Inho Kim
Affiliations:
Seoul National University Hospital,Seoul,Korea, Republic Of
,
Ron Ram
Affiliations:
Rabin Medical Center,Petach Tikva,Israel
,
Jyh-Pyng Gau
Affiliations:
Taipei Veterans General Hospital,Taipei,Taiwan, Province of China
,
Steve Songer
Affiliations:
Celgene Corporation,Summit,United States
,
Lela M. Lucy
Affiliations:
Celgene Corporation,Summit,United States
,
CL Beach
Affiliations:
Celgene Corporation,Summit,United States
Hervé Dombret
Affiliations:
Hôpital Saint Louis, Institut Universitaire d’Hématologie, University Paris Diderot,Paris,France
EHA Learning Center. F.Seymour J. Jun 12, 2015; 99817
John F.Seymour
John F.Seymour

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Abstract
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Abstract: E954

Type: Eposter Presentation

Background
There is no standard treatment (Tx) for older patients (pts) with AML, who have especially poor OS due to adverse risk factors such as unfavorable karyotypes and poor performance status (PS). Older pts may be unfit for high-intensity induction chemotherapy (IC); such pts are often treated with LDAC or best supportive care (BSC) alone, which are associated with very poor outcome (Dombret, Semin Oncol, 2008). The international phase 3 AZA-AML-001 study compared AZA with conventional care regimens (CCR) in older pts with AML. Before randomization, investigators selected their preferred Tx option for each pt from 3 commonly used CCR for AML Tx: IC, LDAC, or BSC only. Pts were then randomized to receive AZA or CCR and received their preselected Tx.

Aims
To compare effects of AZA vs LDAC on OS and clinical outcomes in the subgroup of pts in AZA-AML-001 preselected to receive LDAC before randomization.

Methods
Pts aged ≥65 years with newly diagnosed de novo or secondary AML (>30% bone marrow [BM] blasts by local assessment), ECOG PS 0-2, WBC count ≤15x109/L, and intermediate- or poor-risk cytogenetics were enrolled. AZA dose was 75mg/m2/day SC x7 days/28-day cycle and LDAC dose was 20mg SC BID x10 days/28-day cycle. OS and 1-year survival were estimated using Kaplan-Meier methods. OS was compared between Tx groups by log-rank test. An unstratified Cox proportional hazards model generated hazard ratios (HRs) and 95% CIs. Overall response rate (ORR) included complete remission (CR) + CR with incomplete blood count recovery (CRi) (IWG 2003). Proportions of pts with grade 3-4 infections and hematologic treatment-emergent adverse events (TEAEs), and TEAE incidence rates (IR) per 100 pt-years of Tx exposure, are reported.

Results
Of all pts in AZA-AML-001, most (312/488, 64%) were preselected to receive LDAC (AZA n=154, LDAC n=158). Median number of Tx cycles received was 7 (range 1–28) for AZA and 4 (1–25) for LDAC. At baseline in the AZA and LDAC groups, respectively, median ages were 76 (range 64–90) and 75 (65–88) years; 25% and 22% had ECOG PS of 2; centrally read median BM blasts were 70% (2–100) and 74% (4–100); and 29% and 34% of pts had poor-risk cytogenetics. Median OS in the AZA and LDAC groups was 11.2 vs 6.4 months (mon), respectively (HR=0.90 [95%CI 0.70, 1.16], p=0.43; Figure), indicating a 4.8-mon (95%CI 1.7, 7.9) longer median OS with AZA. The OS difference was not statistically significant due to convergence of the OS curves at ~20 mon. One-year survival rate was 48.5% with AZA vs 34.0% with LDAC, a difference of 14.5% (95%CI 3.5%, 25.5%). ORR was 27% with AZA and 26% with LDAC. Proportions [IRs] of AZA and LDAC pts, respectively, with grade 3-4 TEAEs were: anemia 19% vs 23% [26 vs 42]; neutropenia 25% vs 25% [33 vs 46]; febrile neutropenia 27% vs 30% [36 vs 56]; thrombocytopenia 25% vs 28% [34 vs 51]; and infections 49% vs 46% [66 vs 84].

Summary
Analyzing outcomes within preselection groups allows assessment of Tx effects in pts with generally similar prognoses and clinical features, as preselection of the preferred CCR occurred before randomization. AZA was associated with a longer median OS of 11.2 mon vs 6.4 mon with LDAC, in pts with similar features at study entry. At 1 year, almost one-half of AZA-treated pts were alive, compared with approximately one-third of LDAC-treated pts. Quality of life outcomes during Tx with AZA or LDAC in this pt group are now being evaluated. AZA may offer potential advantages over LDAC as first-line low-intensity Tx in difficult-to-treat older pts with AML and high blast counts.

Keyword(s): Acute myeloid leukemia, Survival



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