Elderly patients with acute myeloid leukemia (AML) generally have a poor prognosis, but maintenance therapy with an androgen, norethandrolone, significantly improved survival in this population, investigators report in the Journal of Clinical Oncology.

The 5-year disease-free survival was almost double in patients who received norethandrolone (31.2% vs 16.2%), and event-free survival (EFS) and overall survival (OS) were also markedly improved.

A number of hypotheses could explain why norethandrolone improves outcomes in this population. “Because androgen supplementation was initiated when the tumoral mass was decreased, it is possible that norethandrolone decreased the proliferation of remaining blast cells and/or their genetic instability in restoring proper telomere length,” wrote Arnaud Pigneux, MD, PhD, of the Centre Hospitalier Universitaire, Bordeaux (France), and his coauthors. “In addition, as in aplastic anemia, a beneficial effect could be exerted by androgens on normal hematopoietic cells recovering after the end of the postinduction aplastic phase,” they said (J Clin Oncol. 2016 Oct 17. doi: 10.1200/JCO.2016.67.6213 )

The majority of patients with AML are older than 60 years of age at the time of their diagnosis, and the prognosis is particularly poor for a number of reasons, including a greater intolerance to intensive chemotherapies and the presence of comorbidities. In addition, older patients also frequently present with unfavorable prognostic features, including multidrug resistant phenotypes or poor-risk cytogenetics.

In this study, Dr. Pigneux and his team enrolled 330 patients with AML de novo or secondary to chemotherapy or radiotherapy, who were 60 years of age or older. Induction therapy of idarubicin 8 mg/m2 on days 1 to 5, cytarabine 100 mg/m2 on days 1 to 7, and lomustine 200 mg/m2 on day 1 was administered.

Those who achieved complete or partial remission received six reinduction courses, alternating idarubicin and cytarabine, and a regimen of methotrexate and mercaptopurine. The cohort was then randomized to receive norethandrolone 10 or 20 mg/day (arm A) according to body weight, or no norethandrolone (arm B) for a 2-year maintenance therapy regimen.

Disease-free survival (DFS) was significantly improved in patients who received androgen therapy, but there was no difference between groups in patients with a high WBC count.

The 5-year DFS was 39.2% for arm A versus 15.1% in arm B for patients with a low WBC count, and 14.3% in arm A versus 20.8% in arm B for patients with a high WBC count.

From the time of inclusion, the 5-year EFS and OS were 21.5% (95% confidence interval, 15.5%-28.1%) and 26.3% (95% CI, 19.7%-33.2%), respectively, in arm A versus 12.9% (95% CI, 8.3%-18.5%) and 17.2% (95% CI, 11.9%-23.4%), respectively, in arm B.

For patients with unfavorable cytogenetics (n = 78), outcomes were better if they received norethandrolone.

The 5-year DFS for this subset was 15.79% in arm A versus 7.69% in arm B. For patients with low- or intermediate-risk cytogenetics, the 5-year DFS was 39.73% in arm A versus 19.72% in arm B.

No funding source was disclosed. Dr. Pigneux has disclosed consulting or advisory roles with Amgen, Celgene, MSD, and Novartis, and disclosed receiving funding for travel and accommodations expenses from Amgen and Pfizer. Several of the authors have disclosed relationships with industry.