San Diego, California—Older patients with newly diagnosed acute myeloid leukemia (AML) had similar outcomes and early mortality regardless of whether they received decitabine in a 5- or 10-day schedule, results from a recent study by Nicholas J. Short, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

Together with his colleagues, Dr Short, who presented the findings at the 2018 ASH Annual Meeting, conducted a phase 2 clinical trial of 71 adults aged ≥60 (median age, 78 years) years between February 2013 and April 2018.

“Single-arm studies have suggested that a 10-day schedule of decitabine may result in better outcomes than the standard 5-day schedule in older patients with AML, particularly in patients with TP53 mutations,” they said, describing the basis for their research.

Patients were eligible for enrollment in the study if they had an Eastern Cooperative Group performance status score 0 to 3, adequate renal and hepatic function, and newly diagnosed AML. Patients aged <60 years for whom intensive chemotherapy was not suitable could also enroll.

The primary end point was response rate, and secondary end points included safety, duration of response, and overall survival (OS). In addition, patients who had the TP53 mutation at baseline underwent single-gene TP53 sequencing in serial samples to track TP53 clones with decitabine, as part of an exploratory analysis.

All patients in the study were randomized to receive decitabine 20 mg/m2 daily for 5 or 10 consecutive days as initial therapy. They were allowed to receive up to 3 courses of decitabine at the randomly assigned dose; however, once they were in remission, they were given consolidation decitabine in a 5-day schedule for up to 24 total cycles. A total of 28 patients received the drug for 5 consecutive days, whereas 43 received it for 10.

The complete remission (CR) rates were similar between both study groups, with 29% in the 5-day arm and 30% in the 10-day arm; likewise, the rates of CR, CR with incomplete platelet recovery, and CR with incomplete hematologic recovery combined were similar between both study groups (43% vs 40%, respectively; P = .78).

Because of the similarity in response rates, Dr Short and colleagues deemed the trial futile and terminated it early.

Of note, there was a trend towards earlier responses with the 10- versus 5-day schedule (P = .09), and there were no significant differences in response rates among patients in the same disease subgroups (ie, cytogenetics, de novo vs secondary AML, or TP53 mutation).

“The 30-day mortality rates for the 5-day and 10-day arms were 4% and 9%, and the 60-day mortality rates were 21% and 25%, respectively,” Dr Short and colleagues reported.

Follow-up lasted a median duration of 38.2 months, and the duration of median remission for the 5- and 10-day arms was 9.4 and 6.4 months, respectively. At 1 year, continuous remission rates were 26% and 33%, respectively (P = .98). 

The median OS was 5.5 and 6.0 months in the 5- and 10-day arms, respectively. At 1 year, OS rates were 25% in both arms (P = .47), and Dr Short and colleagues observed no significant difference in OS between the arms when they stratified the patients into disease subgroups. In addition, the median OS for patients with AML and the TP53 mutation was 5.5 months for the 5-day arm and 4.9 months for the 10-day arm (P = .55).

There were 2 patients in whom the TP53 mutation was no longer detectable posttreatment, despite them having had the mutation at baseline; these 2 patients had been in the 10-day schedule arm, and were the longest survivors among those in the TP53 mutation cohort.

“In older adults with newly diagnosed AML, DAC [decitabine] given for either 5 or 10 consecutive days resulted in similar response rates, early mortality and survival. No differences in response or survival were observed in any subgroup, including TP53-mutated AML,” Dr Short and colleagues concluded.—Hina Khaliq

Short NJ, Kantarjian HM, Loghavi S, et al. Five-day versus ten-day schedules of decitabine in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase II study. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 84.