Treatment with a 5-day versus a 10-day schedule of decitabine in older patients with newly diagnosed acute myeloid leukaemia: a randomised phase 2 trial

Summary Background Hypomethylating agents, such as decitabine, are the standard of care for older patients with newly diagnosed acute myeloid leukaemia. Single-arm studies have suggested that a 10-day schedule of decitabinecycles leads to better outcomes than the usual 5-day schedule. We compared the efficacy and safety of these two schedules. Methods Eligible patients were aged 60 years or older with acute myeloid leukaemia but unsuitable for intensive chemotherapy (or 2 decitabineintravenously for 5 or 10 consecutive days as induction therapy, every 4–8 weeks for up to three cycles. Responding patients received decitabineas consolidation therapyon a 5-day schedule for up to 24 cycles. We assessed a composite primary endpoint of complete remission, complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete haematological recovery (CRi) achieved at any time and assessed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01786343. Findings Between Feb 28, 2013, and April 12, 2018, 71 patients were enrolled. 28 received decitabinefor 5 days and 43 for 10 days, and all were assessable for efficacy and safety. The primary endpoint was achieved in similar proportions of patients in the two treatment groups (12 [43%] of 28 in the 5-day schedule group, 95% credible interval26–60, and 17 [40%] of 43 in the 10-day schedule group, 26–54, p=0·78; difference 3%, −21 to 27). Total follow-up was 38·2 months, during which the median duration of overall survival was 5·5 months (IQR 2·1–11·7) in the 5-day group and 6·0 months (1·9–11·7) in the 10-day group. 1-year overall survival was 25% in both groups. Complete remission, CRp, CRi, and overall survival did not differ between groups when stratified by cytogenetics, de-novo versus secondary or therapy-related acute myeloid leukaemia, or TP53 mut status. The most common grade 3–4 adverse events were neutropenic fever(seven patients [25%] in the 5-day group and 14 [33%] in the 10-day group) and infection (five [18%] and 16 [37%], respectively). One patient (4%) died from sepsis in the context of neutropenic fever, infection, and haemorrhage in the 5-day group, and in the 10-day group six patients (14%) died from infection. Early mortality was similar in the two groups. Interpretation In older patients with newly diagnosed acute myeloid leukaemia, efficacy and safety did not differ by the 5-day or the 10-day decitabineschedule. Funding University of Texas MD Anderson Cancer Center and National Cancer Institute Specialized Programs of Research Excellence.