Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens

BMC Cancer

Research Article

Dominik Selleslag¹  Anna Candoni²  James Cavenagh³  Rajat Kumar⁴  Jerry Weaver⁵  C. L. Beach⁵  Steve Songer⁵  Christian Récher⁶  Richard M. Stone⁷  John F. Seymour⁸  Teresa Bernal del Castillo⁹  Jose Falantes^1,10  Hervé Dombret^1,11  Agnieszka Wierzbowska^1,12  Andre C. Schuh^1,13  Mark D. Minden^1,13  Jun Ho Jang^1,14  Haifa Kathrin Al-Ali^1,15  Irwindeep Sandhu^1,16  Hartmut Döhner^1,17  Aleksandra Butrym^1,18 

[1] Algemeen Ziekenhuis Sint-Jan, Brugge, Belgium;Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy;Barts Health National Health Service Trust, London, UK;Cancer Care Manitoba, Winnipeg, Canada;Celgene Corporation, Summit, NJ, USA;Centre Hospitalier Universitaire de Toulouse, Toulouse, France;Dana-Farber Cancer Institute, Boston, MA, USA;Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett St, 8006, East Melbourne, VIC, Australia;University of Melbourne, Parkville, Australia;Hospital Central de Asturias, Oviedo, Spain;Hospital Universitario Virgen del Rocio/Instituto de BioMedicinia de Sevilla, Sevilla, Spain;Hôpital Saint Louis, Institut Universitaire d’Hématologie, University Paris Diderot, Paris, France;Medical University of Lodz, Lodz, Poland;Princess Margaret Cancer Centre, Toronto, Canada;Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;University Hospital of Halle, Halle, Germany;University of Alberta Hospital, Edmonton, Canada;Universitätsklinikum Ulm, Ulm, Germany;Wroclaw Medical University, Wroclaw, Poland;

关键词: Azacitidine;    Low-dose cytarabine;    Acute myeloid leukaemia;    AML;    Myelodysplasia-related changes;    AML-MRC;    Induction chemotherapy;    Response;    Survival;   

DOI  :  10.1186/s12885-017-3803-6

 received in 2017-08-22, accepted in 2017-11-20,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCompared with World Health Organization-defined acute myeloid leukaemia (AML) not otherwise specified, patients with AML with myelodysplasia-related changes (AML-MRC) are generally older and more likely to have poor-risk cytogenetics, leading to poor response and prognosis. More than one-half of all older (≥65 years) patients in the phase 3 AZA-AML-001 trial had newly diagnosed AML-MRC.MethodsWe compared clinical outcomes for patients with AML-MRC treated with azacitidine or conventional care regimens (CCR; induction chemotherapy, low-dose cytarabine, or supportive care only) overall and within patient subgroups defined by cytogenetic risk (intermediate or poor) and age (65–74 years or ≥75 years). The same analyses were used to compare azacitidine with low-dose cytarabine in patients who had been preselected to low-dose cytarabine before they were randomized to receive azacitidine or CCR (ie, low-dose cytarabine).ResultsMedian overall survival was significantly prolonged with azacitidine (n = 129) versus CCR (n = 133): 8.9 versus 4.9 months (hazard ratio 0.74, [95%CI 0.57, 0.97]). Among patients with intermediate-risk cytogenetics, median overall survival with azacitidine was 16.4 months, and with CCR was 8.9 months (hazard ratio 0.73 [95%CI 0.48, 1.10]). Median overall survival was significantly improved for patients ages 65–74 years treated with azacitidine compared with those who received CCR (14.2 versus 7.3 months, respectively; hazard ratio 0.64 [95%CI 0.42, 0.97]). Within the subgroup of patients preselected to low-dose cytarabine before randomization, median overall survival with azacitidine was 9.5 months versus 4.6 months with low-dose cytarabine (hazard ratio 0.77 [95%CI 0.55, 1.09]). Within the low-dose cytarabine preselection group, patients with intermediate-risk cytogenetics who received azacitidine had a median overall survival of 14.1 months versus 6.4 months with low-dose cytarabine, and patients aged 65–74 years had median survival of 14.9 months versus 5.2 months, respectively. Overall response rates were similar with azacitidine and CCR (24.8% and 17.3%, respectively), but higher with azacitidine versus low-dose cytarabine (27.2% and 13.9%). Adverse events were generally comparable between the treatment arms.ConclusionsAzacitidine may be the preferred treatment for patients with AML-MRC who are not candidates for intensive chemotherapy, particularly patients ages 65–74 years and those with intermediate-risk cytogenetics.Trial registrationThis study was registered at clinicalTrials.gov on February 16, 2010 (NCT01074047).

【 授权许可】

CC BY   
© The Author(s). 2017