One year of maintenance therapy with brief monthly courses of intravenous decitabine was associated with improved overall survival (OS) among older patients with acute myeloid leukemia (AML) who had responded favorably to intensive induction therapy, according to results from an exploratory analysis of the ECOG-ACRIN E2906 trial presented at the 2019 ASH Annual Meeting. The findings appear to support the use of maintenance therapy in eligible patients, lead investigator James M. Foran, MD, of Mayo Clinic in Jacksonville, Florida, told ASH Clinical News, but need to be confirmed in a larger trial.
"This was an exploratory study within a larger phase II trial," Dr. Foran explained. "We had only 120 patients enrolled of the intended 172 because the parent study closed early, so it's a compelling result, but I can't call it a definitive result."
The larger parent study was the prospective, randomized, phase II ECOG-ACRIN E2906 trial, which compared outcomes with standard 7+3 induction or single-agent clofarabine in older adults (aged â‰¥60 years) with relapsed/refractory AML. As researchers reported at the 2017 ASH Annual Meeting, the trial was stopped early, after the data monitoring committee found a survival advantage with 7+3 over clofarabine. Because relapse remains the major cause of treatment failure after complete response (CR) to intensive induction therapy, Dr. Foran and researchers included a second randomization in the E2906 study to determine whether maintenance therapy with abbreviated decitabine could improve outcomes after first CR, compared with observation.
The maintenance therapy investigation included 120 participants who were in CR or CR with incomplete blood count recovery at the time of study suspension. Patients were randomized 1:1 to receive 1 year of decitabine treatment (n=59) or observation (n=61). Decitabine 20 mg/m2 was administered intravenously on days 1 to 3, every 4 weeks. There were no dose reductions allowed, but patients receiving decitabine could hold treatment for up to 4 weeks to allow for hematologic recovery.
Of the 120 enrolled patients (median age = 69 years; range = 60-85), most had intermediate-risk disease (74.2%) and an Eastern Cooperative Oncology Group performance status score of 0 to 1 (96%). Clinical characteristics were well balanced between the 2 groups, the researchers reported.
Patients in the decitabine group received a median of 6 treatment cycles (range = 0-13 cycles). After a median follow-up of 49.8 months, 82 patients had died (46 in the observation group and 36 in the decitabine group), while 90 patients had either relapsed or died and were evaluable for disease-free survival (DFS; 47 in the observation group and 43 in the decitabine group).
In multivariate analysis, OS was significantly improved in the decitabine group (hazard ratio [HR] = 0.65; 95% CI 0.37-1.15; p=0.07), but the improvement in DFS did not reach statistical significance (HR=0.70; 95% CI 0.40-1.21; p=0.1).
The survival advantage with decitabine was greatest in the portion of patients who had FLT3 testing performed at diagnosis and were found to be FLT3-ITD–negative, Dr. Foran noted, for both OS and DFS (p=0.039).
He also reported that, overall, decitabine was "generally well tolerated," apart from incidences of grade 3 neutropenia (9%) and reversible grade 4 cytopenias. No grade 5 events related to decitabine treatment were reported.
"There was no group in our analysis who seemed to do worse with decitabine," Dr. Foran concluded, "but it looks like the biggest advantage may be, at least in our trial, in intermediate-risk, older adults [who are] fit for therapy and do not have a FLT3-ITD mutation."
However, he acknowledged the limitations presented by the incomplete accrual and early discontinuation of the parent study. "It's quite possible that prolonged therapy for more than a year would be helpful, [but] we were obliged to stop at a year because that's what our preliminary data supported at the time," Dr. Foran said. "We are planning to move this [investigation] forward into a definitive trial of patients who are in remission and would be fit for this [approach]."
The authors report no relevant conflicts of interest.
Foran JM, Sun Z, Claxton DF, et al. Maintenance decitabine (DAC) improves disease-free (DFS) and overall survival (OS) after intensive therapy for acute myeloid leukemia (AML) in older adults, particularly in FLT3-ITD-negative patients: ECOG-ACRIN (E-A) E2906 randomized study. Abstract 115. Presented at the 2019 American Society of Hematology Annual Meeting, December 7, 2019; Orlando, FL.