Researchers have found the telomerase inhibitor imetelstat was active in patients with myelofibrosis, but had the potential to cause clinically significant myelosuppression, according to an article published in The New England Journal of Medicine.

Current drugs for myeloproliferative neoplasm-associated myelofibrosis do not induce complete or partial remissions. Imetelstat, a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase reverse transcriptase, was studied in patients with high-risk or intermediate-2-risk myelofibrosis in order to determine therapeutic activity and safety.

A total of 33 patients met the eligibility criteria and 48% had been previously treated with JAK inhibitor therapy. Imetelstat was administered as a 2-hour intravenous infusion (starting dose, 9.4 mg per kilogram of body weight) every 1 to 3 weeks.

Continue Reading

Complete or partial remission occurred in 7 patients (21%), with a median duration of response of 18 months for complete responses and 10 months for partial responses. Bone marrow fibrosis was reversed in all four patients who had a complete response and a molecular response occurred in three of the four patients.

Mutation status affected response rates. Patients with a JAK2 mutation had a response rate of 27% versus those without the mutation (P=0.30), and 32% of patients with an ASXL1 mutation achieved a response versus 0% among those without (P=0.07).

RELATED: In Myelofibrosis, Ruxolitinib Response Associated with Mutation Profile

Complete response was achieved in 38% of patients with a mutation in SF3B1 or U2AF1 versus 4% among patients without a mutation in these genes (P=0.04).

Treatment-related adverse events included grade 4 thrombocytopenia (18% of patients), grade 4 neutropenia (12%), grade 3 anemia (30%), grade 1 or 2 elevation in total bilirubin (12%), alkaline phosphatase (21%), and aspartate aminotransferase (27%).


  1. Tefferi A, Lasho TL, Begna KH, et al. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Eng J Med; 2015;373(10):908-919.