Short NJ, et al. - Researchers investigated which of the two decitabine schedules, a 10-day schedule or a usual 5-day schedule, is more efficacious and safe for treating older patients with newly diagnosed acute myeloid leukaemia. With regard to efficacy and safety, no difference was observed between the 5-day or the 10-day decitabine schedule in this patient population.

Methods

• Sixty years or older acute myeloid leukaemia patients who were unsuitable for intensive chemotherapy (or <60 years if unsuitable for intensive chemotherapy with an anthracycline plus cytarabine) were considered eligible to be included in this study.
• Researchers used computer-generated block randomisation (block size 40) for equal allocation of the first 40 patients to the two treatment groups, thereafter, using all previous patients' treatment and response data, a response-adaptive randomisation algorithm decided the allocation of each following patient favouring the group with superior response.
• They assigned patients to receive 20 mg/m² decitabine intravenously for 5 or 10 consecutive days as induction therapy, every 4–8 weeks for up to three cycles.
• They administered decitabine as consolidation therapy on a 5-day schedule for up to 24 cycles to responding patients.
• By intention to treat analysis, complete remission, complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete haematological recovery (CRi) achieved at any time were evaluated as a composite primary endpoint.

Results

• A total of 71 patients were enrolled between Feb 28, 2013, and April 12, 2018, of those, decitabine was received by 28 for 5 days and 43 for 10 days, and all were assessable for efficacy and safety.
• In the two treatment groups, the proportions of patients achieving primary endpoint were similar (12 [43%] of 28 in the 5-day schedule group, 95% credible interval 26–60, and 17 [40%] of 43 in the 10-day schedule group, 26–54, p=0·78; difference 3%, −21 to 27).
• In the 5-day group and in the 10-day group, the median duration of overall survival observed during 38·2 months of follow-up was 5·5 months (IQR 2·1–11·7) and 6·0 months (1·9–11·7), respectively.
• Both groups showed 25% 1-year overall survival.
• No difference was seen in complete remission, CRp, CRi, and overall survival between groups on stratification by cytogenetics, de-novo vs secondary or therapy-related acute myeloid leukaemia, or TP53 ^mut status.
• 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) were documented as the most common grade 3–4 adverse events experienced.
• Death of 1 patient (4%) was reported due to sepsis in the context of neutropenic fever, infection, and haemorrhage in the 5-day group, and deaths of 6 patients (14%) was reported in the 10-day group, which were attributed to infection.
• Both the groups had similar early mortality.