Imetelstat in intermediate-2 or high-risk myelofibrosis refractory to JAK inhibitor: IMpactMF phase III study design

Future Oncol. 2022 Jul;18(22):2393-2402. doi: 10.2217/fon-2022-0235. Epub 2022 May 5.


Imetelstat, a first-in-class telomerase inhibitor, demonstrated meaningful clinical benefit including a robust symptom response rate and potential overall survival benefit in IMbark, a phase II study in intermediate-2 or high-risk myelofibrosis (MF) patients who have relapsed after or are refractory to JAK inhibitors. We describe the rationale and design for the phase III trial, IMpactMF (NCT04576156), an open-label evaluation of imetelstat versus best available therapy, excluding JAK inhibitors, in MF patients refractory to JAK inhibitor. Imetelstat 9.4 mg/kg is administered as an intravenous infusion every 21 days. Primary objective is to assess overall survival. Secondary objectives include symptom and spleen responses, progression-free survival, clinical response assessment, bone marrow fibrosis reduction, safety and pharmacokinetics. Biomarker, cytogenetics and mutation analyses will be performed.

Keywords: JAK inhibitor; biomarkers; fedratinib; imetelstat; myelofibrosis; pacritinib; ruxolitinib; safety; survival; telomerase.

Plain language summary

Imetelstat is a new type of treatment being studied in patients with myelofibrosis (MF). Encouraging clinical benefits were seen in a phase II clinical trial of imetelstat in higher risk MF. This article discusses the ongoing phase III trial, called IMpactMF. IMpactMF is comparing imetelstat to best available therapy (BAT) in MF patients not responding to a specific type of treatment, a JAK inhibitor. Imetelstat is an intravenous infusion, given every 21 days. This study will determine if patients who receive imetelstat live longer than patients who are given BAT. It will also collect information on additional outcomes, including safety. Trial Registration Number: NCT04576156 (

Publication types

  • Review

MeSH terms

  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Humans
  • Janus Kinase Inhibitors*
  • Nitriles / therapeutic use
  • Oligonucleotides
  • Primary Myelofibrosis* / diagnosis
  • Primary Myelofibrosis* / drug therapy
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects


  • Janus Kinase Inhibitors
  • Nitriles
  • Oligonucleotides
  • Pyrazoles
  • Pyrimidines
  • imetelstat

Associated data


Grant support