Background: Compared 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.

Methods: We 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).

Results: Median 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.

Conclusions: Azacitidine 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 registration: This study was registered at clinicalTrials.gov on February 16, 2010 (NCT01074047 ).

Ethics approval and consent to participate

The AZA-AML study design was approved by the institutional review boards or independent ethics committees at each study site, and was conducted in accordance with the ethical principles set forth in the Declaration of Helsinki. All patients provided written informed consent before study participation.

Consent for publication

Not applicable.

Competing interests

J.F.S.: consultancy for AbbVie, Celgene, Genentech, Gilead, Janssen, Roche, Takeda; research funding from AbbVie and Janssen; honoraria from AbbVie, Celgene, Genentech, Gilead, Janssen, Roche, Takeda; speakers’ bureau fees from AbbVie, Celgene, Gilead, Janssen, Roche; and advisory board participation for AbbVie, Celgene, Genentech, Gilead, Janssen, Roche, Takeda. H. Döhner: advisory boards (with honoraria) for Agios, Amgen, Astex Pharmaceuticals, Celator, Celgene, Novartis, Roche, Seattle Genetics, Sunesis, and Tolero. A.W.: honoraria from Celgene. D.S.: honoraria and consultancy, Celgene and Johnson & Johnson; research funding, Celgene. R.K.: consultancy and advisory board participation for Celgene. J.C.: advisory boards and/or speakers’ bureaus for Celgene, Janssen and Novartis. A.C.: consultancy and speakers’ bureau participation for Celgene. C.R.: honoraria, research funding and consultancy, Celgene, Sunesis, Amgen, and Novartis; honoraria and consulting fees from Pfizer and Jazz Pharmaceuticals. I.S.: consultancy and honoraria from Celgene. H.K.A.: consultancy, honoraria and research funding from Celgene; consultancy, Otsuka. J.F.: consultancy for Celgene. R.M.S.: advisory board participation and consultancy for AbbVie, Actinium, Agios, Amgen, Arog, Astellas, Celgene, Cornerstone, Fujifilm, Janssen, Jazz, Karyopharm, Merck, Novartis, Ono, Orsenix, Otsuka, Pfizer, Roche, Seattle Genetics and Sumitomo; clinical research funding from Agios, Novartis and Arog; DSMB participation for Argenix and Celgene. J.W., S.S., and C.L.B. are Celgene employees and own Celgene stock. H. Dombret: consultancy for Amgen and Celgene; honoraria from Agios, Ambit, Amgen, Ariad, Astellas, Celgene, Janssen, Jazz, Karyopharm, Kite Pharma, Menarini, Novartis, Pfizer, Roche/Genentech, Seattle Genetics and Servier; research funding from Amgen, Ariad, Jazz Pharma, Kite Pharma, and Roche/Genentech. A.B., J.H.J., T.B., M.D.M. and A.C.S.: nothing to disclose.

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