Effects of nandrolone decanoate on telomere length and clinical outcome in patients with telomeropathies: a prospective trial

Androgens have been reported to elongate telomeres in retrospective and prospective trials with patients with telomeropathies, mainly with bone marrow failure. In our single-arm prospective clinical trial, 17 patients with short telomeres and/or germline pathogenic variants in telomere-biology genes associated with at least one cytopenia and/or radiologic diagnosis of ILD were treated with 5 mg/kg of intramuscular nandrolone decanoate every 15 days for 2 years. Ten of 13 evaluable patients (77%) showed telomere elongation at 12 months by flow-FISH (average increase, 0.87 kb; 95% CI, 0.20-1.55 kb; p=0.01). At 24 months, all 10 evaluable patients showed telomere elongation (average increase, 0.49 kb; 95% CI, 0.24-1.23 kb; p=0.18). Hematologic response was achieved in 8/16 patients (50%) with marrow failure at 12 months, and in 10/16 patients (63%) at 24 months. Seven patients had ILD at baseline, and two and three had pulmonary response at 12 and 24 months, respectively. Two patients died due to pulmonary failure during treatment. In the remaining evaluable patients, the pulmonary function remained stable or improved, but showed consistent decline after cessation of treatment. Somatic mutations in myeloid neoplasm-related genes were present in a minority of patients and were mostly stable during drug treatment. The most common adverse events (AE) were elevations in liver function test levels in 88%, acne in 59%, and virilization in 59%. No AE grade ≥ 4 was observed. Our findings indicate that nandrolone decanoate elongates telomeres in patients with telomeropathies, which correlated with clinical improvement in some cases and tolerable adverse events. ClinicalTrials.gov Identifier: NCT02055456.