A Randomized Open-Label Study To Evaluate The Efficacy Of Azacitidine For Post-Remission Therapy Of Acute Myeloid Leukemia In Elderly Patients (QOLESS AZA-AMLE)

![Graphic][1] Background The incidence of acute myeloid leukemia (AML) increases with age. In elderly AML patients, intensive chemotherapy has been associated with complete remission (CR) rates of approximately 45%, considerably lower than in younger patients; the duration of remission is shorter and the early treatment-related mortality is high, 30% to 50%, which partially explains a median survival of 7 to 12 months. Several studies have suggested that maintenance therapy may improve CR duration and long-term, disease-free survival (DFS). Grovdal et al (2010) treated 60 elderly patients with high-risk myelodysplastic syndrome (MDS) or AML with cytarabine-based induction therapy resulting in CR in 24 patients who continued on to 5-Azacitidine (5-Aza) maintenance therapy. The median duration of complete response was 13.5 months. The median OS for the 5-Azacitidine-treated group was 20 months. Aims The present phase III, prospective, randomized, open-label, multicenter trial is designed to assess the efficacy of post-remission treatment with 5-Aza versus best supportive care in a cohort of subjects of > 60 years of age with AML, and in CR after conventional induction (“3+7”) and consolidation chemotherapy. Primary objectives are to evaluate overall survival overall survival and DFS at 2 years; secondary objectives are to evaluate the number and length of hospitalizations in the 2 arms in the 2-year post-remission period. Methods Approximately 95 patients with the following criteria: newly diagnosed AML with > 30% myeloid marrow blasts, either “de novo” or evolving from a MDS not previously treated with chemotherapeutic agents; no contraindications for intensive chemotherapy and performance status<3 will be included. Thirty-eight patients will be randomized in the post-remission phase 1:1. Standard induction chemotherapy consists of two courses of 3 + 7 with Daunorubicin at a daily dosage of 40 mg/m2 for 3 days (days 1-3) in combination with 100 mg/m2 cytarabine per day as a continuous IV infusion for 7 days (days 1-7). Consolidation consists of cytarabine 800 mg/m2 3 hour infusion bid (days 1-3). Patients in CR are randomized 1:1 to receive best supportive care (BSC) or 5-Aza according to the following schema: 50 mg/sqm s.c. or i.v. for 7 days every 28 days and increase after 1st cycle, if well tolerated, to 75 mg/m2 s.c or i.v. for 7 days (5 + weekend off + 2) every 28 days for further 5 cycles, followed by 6 cycles every 56 days for 2 years post-remission. Results At the time of the present report 58 patients have been included in the study. Median age at diagnosis was 72, interquartile range (IQR) 65-75 years, M/F 34/24. During induction-consolidation chemotherapy, 16 patients were relapsed/refractory, 9 patients died, 3 patients were excluded for protocol violation, 3 refused to continue and 8 have not yet reached consolidation treatment. Nineteen patients have been randomized; characteristics of patients are shown in the [table][2]. Eighteen patients have reached at least a 4 week follow-up. Amongst these, 11 patients are still in CR at a median observation time of 25.4, IQR 12.9-47.4 weeks. Five patients in the BSC arm have experienced AML recurrence at 7, 8, 13, 21, 49 weeks, respectively, verus 2 patients in the 5-Aza arm at 42 and 47 weeks. DFS is longer in the 5-Aza arm ([Figure][3]). Grade 3-4 adverse events included neutropenia in 2 cases in the 5-Aza arm and in 1 case in the BSC arm. There were no hospitalizations related to the adverse events in either arm. View this table: Table. Characteristics of patients at randomization, in CR after induction-consolidation chemotherapy. ![Figure.][4] Figure. Disease-free survival in the post-remission phase. Conclusions Preliminary results suggest that in elderly AML patients receiving standard induction-consolidation chemotherapy, 5-Aza post-CR is well-tolerated and may prolong survival. Disclosures: Oliva: Celgene: Consultancy. Off Label Use: Azacitidine is indicated for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with: • intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS), • chronic myelomonocytic leukaemia (CMML) with 10-29 % marrow blasts without myeloproliferative disorder, • acute myeloid leukaemia (AML) with 20-30 % blasts and multi-lineage dysplasia, according to World Health Organisation (WHO) classification. [1]: /embed/inline-graphic-2.gif [2]: #T1 [3]: #F1 [4]: pending:yes