Authors: Lisa Pleyer Sonja Burgstaller Michael Girschikofsky Werner Linkesch Reinhard Stauder Michael Pfeilstocker Martin Schreder Christoph Tinchon Thamer Sliwa Alois Lang Wolfgang R Sperr Peter Krippl Dietmar Geissler Daniela Voskova Konstantin Schlick Josef Thaler Sigrid MachherndlSpandl Georg Theiler Otto Eckmüllner Richard Greil
Publish Date: 2014/06/21
Volume: 93, Issue: 11, Pages: 1825-1838
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 offlabel in these patients We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry clinicaltrialsgov 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 AZA001 trial which led to European Medicines Agency EMA approval of azacitidine for highrisk 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 MDSIWG2006 response criteria respectively Median OS was 96 95 CI 853–107 months A clinically relevant OS benefit was observed with any form of disease stabilization marrow stable disease 81 months hematologic improvement HI 97 months or the combination thereof 189 months as compared to patients without response and/or without disease stabilization 32 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 diseasemodifying drugs as well as the responserelated factors hematologic improvement and further deepening of response after first response were significant independent predictors of OS in multivariate analysis Azacitidine seems effective in WHOAML including patients with 30 BM blasts currently offlabel 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 azacitidineAcute myeloid leukemia AML is an aggressive disease with an unfavorable prognosis 1 2 Treatment with curative potential ie conventional chemotherapy and/or allogeneic stem cell transplantation is rarely an option for elderly patients due to high age comorbidities poor performance status and/or adverse cytogenetics Azacitidine is approved for AML with 20–30 bone marrow BM blasts Approval was based on the pivotal AZA001 trial 3 4 Currently the 001followup trial clinicaltrialsgov identifier NCT01074047 is underway with the same design but limited to patients with 30 BM blasts with the aim to widen the indication of azacitidine to AML patients as defined by WHO ie irrespective of BM blast count Until the results of this trial become available treatment of AML patients with more than 30 BM blasts with azacitidine remains an offlabel use
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