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Blood Adv. 2018 Apr 24;2(8):923-932. doi: 10.1182/bloodadvances.2018016121.

Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort.

Author information

1
Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
2
Department of Biostatistics, Yale School of Public Health, New Haven, CT.
3
Department of Medicine, University of Valencia, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
4
Section of Hematology, Saint-Louis Hospital, University Paris 7, Paris, France.
5
Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY.
6
Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
7
Massachusetts General Hospital Cancer Center, Department of Hematology/Oncology, Harvard Medical School, Boston, MA.
8
Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL.
9
Division of Oncology & Hematology, University of Nebraska Medical Center, Omaha, NE.
10
Division of Hematology, Mayo Clinic, Rochester, MN.
11
Cote d'Azur University, Nice Sophia Antipolis University, Centre Hospitalier Universitaire de Nice, Nice, France.
12
Division of Hematology, University of Florence, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
13
Department of Pharmacy, Yale New Haven Hospital, New Haven, CT.
14
Department of Hematology, Institut Paoli Calmettes, Marseille, France.
15
Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
16
Section of Hematology, Hospital San Pedro Alcántara, Cáceres, Spain; and.
17
Section of Hematology, University Hospital Reina Sofia, Cordoba, Spain.

Abstract

Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

PMID:
29685952
PMCID:
PMC5916007
DOI:
10.1182/bloodadvances.2018016121
[Indexed for MEDLINE]
Free PMC Article

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