ATLANTA – In older patients with acute myeloid leukemia (AML) in complete remission after intensive chemotherapy, the addition of maintenance therapy with azacitidine significantly improved disease-free survival (DFS), according to results of a randomized, placebo-controlled phase 3 study.
Compared with observation, DFS was significantly improved in the maintenance azacitidine arm, according to results from the 116-patientpresented at the annual meeting of the American Society of Hematology.
Overall survival was not significantly different between arms, possibly because of an excess of allogeneic transplant in the observation arm, according to, of the department of hematology, University Medical Center Groningen, the Netherlands.
“When censored for allogeneic transplant, maintenance with azacitidine improves overall survival,” Dr. Huls said during an oral presentation on the findings.
The randomized maintenance therapy trial was designed to include 126 patients aged 60 years or older who had a confirmed diagnosis of AML and refractory anemia with excess of blasts (RAEB, RAEB-t) and who were in complete remission or in complete remission with incomplete blood count recovery after two cycles of therapy.
Investigators randomly assigned 116 patients to maintenance versus observation. Researchers intended to assign a total of 126 patients, but the trial was stopped early because of slow accrual, Dr. Huls said.
Maintenance treatment with azacitidine was given until relapse for no more than 12 cycles, according to the study protocol. Disease-free survival, the primary endpoint, was measured from the date of randomization to relapse or death from any cause.
Azacitidine maintenance therapy significantly improved DFS (P = .03), Dr. Huls said. After researchers adjusted for poor risk cytogenetic abnormalities at diagnosis and platelet count at study entry, the DFS difference remained significant (hazard ratio, 0.61; 95% confidence interval, 0.4-0.92; P = .019).
Overall survival, a secondary endpoint of the trial, was not significantly different between arms, even after adjustment for cytogenetic abnormalities and platelet counts, Dr. Huls said.
However, investigators found an excess of allogeneic transplant in the observation arm (11 patients, vs. 3 in the azacitidine arm). After they censored those 14 patients, they saw a difference in overall survival favoring azacitidine maintenance that approached significance (P = .07).
Dr. Huls speculated that the excess of transplant may have been related to “the psychology of the doctors.” In the maintenance arm, the physician’s thought process may have been that “ ‘this patient has now had two lines of treatment and has a relapse, and we are done,’ and in the [observation] arm he says, ‘well, the patient has had one arm of treatment, let’s go for another,’ ” Dr. Huls said.
Tolerability data showed that 14 adverse events were reported in the azacitidine maintenance arm, versus 4 for observation. One serious adverse event of grade 3 was reported in the azacitidine arm. The proportion of patients without platelet transfusions during the study was 86% for azacitidine and 93% for observation, and the proportion of patients without red blood cell transfusions was similarly 86% and 92% for the azacitidine and observation arms, respectively.
Dr. Huls reported financial relationships with Janssen and Celgene.
SOURCE: Huls G et al. ASH 2017 .