As reported in NEJM Evidence by Sasaki et al, extended follow-up of a phase II trial showed good outcomes with low doses of the hypomethylating agents decitabine and azacitidine in previously untreated patients with lower-risk myelodysplastic syndromes (MDS).
Study Details
The study included 113 patients with low/intermediate-1 risk on the International Prognostic Scoring System enrolled at The University of Texas MD Anderson Cancer Center between November 2012 and February 2016. They were randomly assigned using a Bayesian response-adaptive design to receive decitabine at 20 mg/m2 daily (n = 73) or azacitidine at 75 mg/m2 daily (n = 40) on days 1 to 3 in 28-day cycles. Due to higher rates of response among the first 20 patients enrolled, the adaptive randomization assigned more patients to the decitabine group. Treatment could be continued indefinitely in patients with response.
Key Findings
Median follow-up for the current analysis was 68 months (range = 2.7–84.1 months). The median number of treatment cycles was 15 (range = 3–74).
Among all 113 patents, response was observed 68 (60%), including 49 (67%) of 73 in the decitabine group and 19 (48%) of 40 in the azacitidine group (P = .042). Complete response rates were 36% among all patients, 36% in the decitabine group, and 35% in the azacitidine group.
Among 59 patients with baseline transfusion dependence, 19 (32%) achieved transfusion independence, including 16 (41%) of 39 in the decitabine group and 3 (15%) of 20 in the azacitidine group (P = .039). Among the 19 patients achieving transfusion independence, median duration of independence was 22 months. Among 54 patients who were transfusion-independent at baseline, 5 (9%) became transfusion-dependent after therapy, including 4 (12%) in the decitabine group and 1 (5%) in the azacitidine group.
No early deaths were observed. Among all patients, median event-free survival was 17 months and median overall survival was 33 months. For the decitabine vs azacitidine groups, median event-free survival was 20 vs 13 months, with 5-year rates of 21% vs 18% (P = .129). Median overall survival was 37 months vs 30 months, with 5-year rates of 33% vs 32% (P = .625).
The investigators concluded, “Attenuated dose treatment of hypomethylating agents in patients with lower-risk MDS can improve outcomes without dose-limiting side effects in a high-risk cohort as defined by the Lower-Risk Prognostic Scoring System.”
Guillermo Garcia-Manero, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the NEJM Evidence article.
Disclosure: The study was funded by grants from the National Cancer Institute and others. For full disclosures of the study authors, visit evidence.nejm.org.
