ASH 2018 | Randomized phase II study comparing 5-day and 10-day decitabine schedule in newly diagnosed acute myeloid leukemia

Nicolas Short from the MD Anderson Cancer Center, Houston, US, presented data at the 60^th American Society of Hematology  Annual Meeting & Exposition, data from a randomized phase II study, which is evaluating the relative safety and efficacy of two different schedules of decitabine, 5-day and 10-day, in older patients with newly diagnosed acute myeloid leukemia (AML).

In this study, 40 patients with newly diagnosed AML were first enrolled and randomized equally to receive decitabine at a daily dose of 20 mg/m² intravenously for either 5 or 10 consecutive days as induction. An adaptive algorithm was adopted to favor the arm with a higher composite response rate. In total, 71 patients have been enrolled in the 5-day (n = 28; median age = 77 years) and 10-day (n = 43; median age = 78 years) arm.  TP53 mutations were detected in 7/24 patients (29%) in the 5-day arm and in 17/41 patients (41%) in the 10-day arm.

The primary endpoint was the composite response (complete remission [CR] + CR with incomplete platelet count [CRp] + CR with incomplete count recovery [CRi]) rates of the two decitabine schedules. The secondary endpoints included the response duration, overall survival (OS) and the safety of the two schedules.

Key findings:

• Data below is representative of 5-day and 10-day arms, respectively
  • Composite response: 43% (12/28) vs 40% (17/43), P = 0.78
  • CR rate: 29% (8/28) vs 30% (13/43), P = 0.88
  • Median follow-up = 38.2 months
  • Median duration of CR: 9.4 vs 6.4 months, P = 0.98
  • Median OS: 5.5 vs 6.0 months, P = 0.47
  • Median OS in TP53-mutation positive patients: 5.5 vs 4.9 months, P = 0.55
  • 30-day mortality rates: 4% vs 9%, P = 0.36
  • 60-day mortality rates: 21% vs 25%, P = 0.69
• There was a trend towards higher TP53 variant allele frequency (VAF) in responders compared to non-responders, P = 0.07
• Responding patients had a significant decline in TP53VAF at the end of cycle 1, P < 0.001
• Two patients with undetectable TP53 had the longest CR duration

The composite response rate between the 5-day and 10-day arms were very similar with a difference of 3%. As a result, the trial was terminated early due to “futility.” However, the findings of this study demonstrate that in older patients with newly diagnosed AML, decitabine given for either 5 or 10 consecutive days resulted in similar response rates, early mortality, and survival.  There were no differences in response or survival were observed in any subgroup, including TP53-mutated AML.

Nicolas Short concluded by stating that decitabine given for 5 consecutive days and 10 consecutive days are “reasonable non-intensive backbone for combination, investigational regimens.”