Phase 3 IMpactMF Trial Evaluating Imetelstat in R/R Myelofibrosis Is Discontinued

The phase 3 IMpactMF trial (NCT04576156) evaluating imetelstat (Rytelo) in patients with intermediate-2– or high-risk myelofibrosis that is relapsed or refractory to a JAK inhibitor is being discontinued following a recommendation from an independent data monitoring committee (IDMC) suggesting that the study is unlikely to meet the primary end point of overall survival (OS) compared with best available therapy (BAT).¹

Based on the IDMC's recommendation, the company decided to stop the trial; the news release did not specify whether the recommendation followed a planned interim analysis. No efficacy data from the study have been reported. The trial had enrolled 327 patients, and its primary completion had previously been anticipated in 2028.^1,2

Regarding safety, the IDMC observed no new safety signals from the known safety profile of imetelstat.¹

Geron plans to conduct a detailed analysis of the IMpactMF data and share the findings with the scientific community at a future date.¹

"Given the recommendation from the [IDMC], we believe discontinuing our phase 3 IMpactMF trial at this time is the right course of action. We are deeply grateful to the patients and families, as well as the investigators and clinical teams whose dedication made this research possible,” Joseph E. Eid, MD, executive vice president of research and development and chief medical officer of Geron, stated in a news release. “Hematologic malignancies are complex diseases, with distinct biological characteristics and treatment challenges across patient populations. We remain committed to thoroughly evaluating the data, understanding what we can learn, and sharing insights that may help inform future research and address the significant unmet needs that remain.”

Imetelstat is approved by the FDA for the treatment of adult patients with low- to intermediate-1–risk myelodysplastic syndromes(MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents.³

How was IMpactMF designed?

The randomized, open-label, multicenter phase 3 IMpactMF trial was initiated in April 2021 and enrolled patients at least 18 years of age with primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis classified as intermediate-2 or high risk per the Dynamic International Prognostic Scoring System.² Patients were required to have disease that was relapsed or refractory to a JAK inhibitor, be ineligible for allogeneic stem cell transplantation, have measurable splenomegaly (a palpable spleen at least 5 cm below the left costal margin or spleen volume of at least 450 cm³ by MRI or CT), have active symptoms with a score of at least 5 on the Myelofibrosis Symptom Assessment Form version 4.0, and have an ECOG performance status of 0 to 2. Patients with peripheral blood or bone marrow blasts of at least 10% and those previously treated with imetelstat were excluded.

Following a 14-day washout from prior therapies, including JAK inhibitors, patients were randomly assigned 2:1 to receive imetelstat at 9.4 mg/kg intravenously every 3 weeks or BAT.^1,2 Patients in the BAT arm who met progressive disease criteria could cross over to imetelstat with sponsor approval.²

Along with the primary end point of OS, secondary end points included symptom response rate (at least a 50% reduction in total symptom score at week 24), progression-free survival, spleen response rate (at least a 35% reduction in spleen volume at week 24), complete remission, partial remission, clinical improvement, and anemia response per modified 2013 International Working Group–Myeloproliferative Neoplasms Research and Treatment criteria, reduction in bone marrow fibrosis, safety, pharmacokinetics, and patient-reported outcomes.

References

1. Geron Corporation provides update on phase 3 IMpactMF clinical trial of imetelstat in relapsed/refractory myelofibrosis. News release. Geron Corporation. October 28, 2026. Accessed October 28, 2026. https://ir.geron.com/news-releases/news-release-details/geron-corporation-provides-update-phase-3-impactmf-clinical
2. A study comparing imetelstat versus best available therapy for the treatment of intermediate-2 or high-risk myelofibrosis (MF) who have not responded to Janus kinase (JAK)-inhibitor treatment. ClinicalTrials.gov. Updated July 8, 2026. Accessed October 28, 2026. https://clinicaltrials.gov/study/NCT04576156
3. FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. FDA. June 6, 2024. Accessed October 28, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imetelstat-low-intermediate-1-risk-myelodysplastic-syndromes-transfusion-dependent