Azacitidine or intensive chemotherapy for older patients with secondary or therapy-related acute myeloid leukemia

Abstract

// Pierre-Yves Dumas 1,2,3,* , Sarah Bertoli 4,5,6,* , Emilie Bérard 7,8 , Clémence Médiavilla 1 , Edwige Yon 7 , Suzanne Tavitian 4 , Thibaut Leguay 1 , Françoise Huguet 4 , Edouard Forcade 1 , Noël Milpied 1,2,3 , Audrey Sarry 4 , Mathieu Sauvezie 1 , Pierre Bories 9 , Arnaud Pigneux 1,2,3,** and Christian Récher 4,5,6,** 1 Service d’Hématologie Clinique et de Thérapie Cellulaire, Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Bordeaux, France 2 Université de Bordeaux, France 3 U1035 INSERM, Bordeaux, France 4 Service d’Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France 5 Université Toulouse III Paul Sabatier, Toulouse, France 6 Cancer Research Center of Toulouse, UMR1037-INSERM, ERL5294-CNRS, Toulouse, France 7 Service d’Epidémiologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France 8 UMR 1027, INSERM-Université de Toulouse III, Toulouse, France 9 Oncomip Network, Réseau de Cancérologie de Midi-Pyrénées, Toulouse, France * These authors have contributed equally to this work ** These authors are co-senior authors Correspondence to: Christian Récher, email: // Keywords : therapy-related acute myeloid leukemia, secondary AML, azacitidine, intensive chemotherapy, older patients Received : September 14, 2016 Accepted : February 27, 2017 Published : March 07, 2017 Abstract The treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.5% post-myelodysplastic syndrome, 17.4% post-myeloproliferative neoplasia, and 45.1% therapy-related acute myeloid leukemia. Patients treated by chemotherapy had less adverse cytogenetics, higher white blood-cell counts, and were younger: the latter two being independent factors entered into the multivariate analyses. Median overall-survival times with chemotherapy and azacitidine were 9.6 (IQR: 3.6−22.8) and 10.8 months (IQR: 4.8−26.4), respectively ( p = 0.899). Adjusted time-dependent analyses showed that, before 1.6 years post-treatment, there were no differences in survival times between chemotherapy and azacitidine treatments whereas, after this time-point, patients that received chemotherapy had a lower risk of death compared to those that received azacitidine (adjusted HR 0.61, 95%CI: 0.38−0.99 at 1.6 years). There were no interactions between treatment arms and secondary acute myeloid leukemia subtypes in all multivariate analyses, indicating that the treatments had similar effects in all three subtypes. Although a comparison between chemotherapy and azacitidine remains challenging, azacitidine represents a valuable alternative to chemotherapy in older patients that have secondary acute myeloid leukemia because it provides similar midterm outcomes with less toxicity.