title: Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group.
abstract: Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20-30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53-10.7) months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.
authors.affiliation: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Hospital Salzburg, and Center for Clinical Cancer and Immunology Trials at Salzburg Cancer Research Institute, Müllner Hauptstrasse 48, 5020, Salzburg, Austria, l.pleyer@salk.at.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pleyer
authors.forename: Sonja
authors.initials: S
authors.lastname: Burgstaller
authors.forename: Michael
authors.initials: M
authors.lastname: Girschikofsky
authors.forename: Werner
authors.initials: W
authors.lastname: Linkesch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Stauder
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeilstocker
authors.forename: Martin
authors.initials: M
authors.lastname: Schreder
authors.forename: Christoph
authors.initials: C
authors.lastname: Tinchon
authors.forename: Thamer
authors.initials: T
authors.lastname: Sliwa
authors.forename: Alois
authors.initials: A
authors.lastname: Lang
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Peter
authors.initials: P
authors.lastname: Krippl
authors.forename: Dietmar
authors.initials: D
authors.lastname: Geissler
authors.forename: Daniela
authors.initials: D
authors.lastname: Voskova
authors.forename: Konstantin
authors.initials: K
authors.lastname: Schlick
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
authors.forename: Sigrid
authors.initials: S
authors.lastname: Machherndl-Spandl
authors.forename: Georg
authors.initials: G
authors.lastname: Theiler
authors.forename: Otto
authors.initials: O
authors.lastname: Eckmüllner
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001317:Austria / Q000453:epidemiology; D001374:Azacitidine / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014944:World Health Organization
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine