Imetelstat shows promise for improving overall survival (OS) and symptoms in patients with high-risk myelofibrosis (MF) that has relapsed or is refractory to Janus kinase (JAK) inhibitors. The phase 3 IMpactMF trial has enrolled more than 70% of total participants and hopes to confirm these benefits, with results expected by 2027.
John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai, New York, presented the rationale and methodology for the ongoing global phase 3 IMpactMF trial (NCT04576156). MF has limited treatment options, and patients with MF that has relapsed or is refractory to JAK inhibitors have a median OS of 13 months.1 Dr. Mascarenhas stressed that the poor survival in this population demonstrates an urgent need for treatment options with alternative mechanisms of action. Imetelstat is a competitive telomerase inhibitor that is FDA approved for specific myelodysplastic syndromes, and phase 2 data indicate tolerability and improved OS at 9.4 mg/kg compared with other doses.2
IMpactMF is an open-label randomized trial for the treatment of MF in patients with intermediate-2 or high-risk MF that has relapsed or is refractory to JAK inhibitors who are ineligible for allogeneic stem cell transplantation.3 Patients are randomly assigned 2:1 to either imetelstat or the best available therapy. The primary endpoint is OS, and the secondary endpoints include symptom response rate and spleen response rate at week 24. The study is still actively recruiting at 172 sites worldwide, with more than 70% of participants enrolled. An interim analysis is planned for when approximately 35% of study participants have died, which is expected in 2026. Final data analysis will be conducted when more than 50% of the enrolled patients have died, which could begin as early as the beginning of 2027.2
REFERENCES
1 Kuykendall AT, Shah S, Talati C, et al. Between a rux and a hard place: evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation. Ann Hematol. 2018;97(3):435-441. doi: 10.1007/s00277-017-3194-4
2 Mascarenhas J, Komrokji RS, Palandri F, et al. Randomized, single-blind, multicenter phase II study of two doses of imetelstat in relapsed or refractory myelofibrosis. J Clin Oncol. 2021;10;39(26):2881-2892. doi: 10.1200/JCO.20.02864
3 Mascarenhas JO, Harrison, Bose P, et al. Imetelstat versus best available therapy in patients with intermediate-2 or high-risk myelofibrosis relapsed or refractory to Janus kinase inhibitor in IMpactMF, a randomized, open-label, phase 3 trial. Abstract #1808.1. Presented at the ASH Annual Meeting; December 7-10, 2024; San Diego, California.