A multicenter phase II trial of Decitabine as first-line treatment of older AML patients judged unfit for induction chemotherapy

Background. Acute myeloid leukemia of older, medically non-fit patients still poses a highly unmet clinical need, and only few large prospective studies have been performed in this indication. With the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine (Decitabine) in MDS and acute myeloid leukemia with 20-30% bone marrow blasts, we asked whether this drug is also active in patients with >30% blasts.Design and Methods. To evaluate efficacy and toxicity of Decitabine in untreated acute myeloid leukemia patients >60 years ineligible for induction chemotherapy, 227 patients (median age 72 years), many with comorbidities, adverse cytogenetics and/or preceding myelodysplastic syndrome (MDS) were treated. During the initial Decitabine treatment (135 mg/m2 total dose infused intravenously over 72 hours every 6 weeks), a median of 2 cycles was administered (range 1-4). All-trans retinoic acid was administered to 100 patients during course 2. Fifty-two patients completing 4 cycles of treatment subsequently received a median of 5 maintenance courses (range 1-19) with a lower dose of Decitabine (20 mg/m2) infused over 1 hour on 3 consecutive days every 4-6 weeks.Results. The complete and partial remission rate was 26% (95% CI: 20%, 32%), an antileukemic effect was noted in 26%. Response rates did not differ between patients with or without adverse cytogenetics; patients with monosomal karyotypes responded also. Median overall survival from start of Decitabine was 5.5 months (range, 0-57.5+), 1-year survival 28% (95%CI: 22%, 34%). Toxicities were predominantly hematologic.Conclusions. Decitabine is well tolerated by older, medically non-fit acute myeloid leukemia patients, myelosuppression being the major toxicity. Response rate and overall survival were not adversely influenced by poor-risk cytogenetics or MDS. Because of these encouraging results, randomized studies evaluating single-agent Decitabine versus conventional treatment are warranted. The study is registered with WHO primary registry German Clinical Trials Registry, number DRKS00000069.status: publishe