Imetelstat Yields Statistically Significant/Clinically Meaningful Improvement in Transfusion in Low-Risk MDS


Imetelstat demonstrated clinically meaningful and statistically significant improvement in transfusion independence at 24 weeks among patients with myelodysplastic syndrome in the phase 3 IMerge trial.

Investigators of the phase 3 IMerge trial (NCT02598661) reported that imetelstat met the primary end point of red blood cell transfusion independence (TI) at 8 weeks in patients with lower risk myelodysplastic syndrome (MDS) who were ineligible to receive erythropoiesis stimulating agents, according to a press release from Geron.

In the IMerge trial, the primary end point of 8-week TI was observed in 39.8% (95% CI, 30.9%-49.3%) of patients treated with imetelstat vs 15.0% (95% CI, 7.1%-26.6%) of those who received placebo (P <.001). Additionally, 24-week TI was observed in 28.0% (95% CI, 20.1%-37.0%) and 3.3% (95% CI, 0.4%-11.5%) of patients in the imetelstat and placebo cohorts, respectively (P <.001).

“The results from the phase 3 IMerge study were resoundingly positive, presenting compelling durability of transfusion independence, delivering on the promise of imetelstat and telomerase inhibition for these patients,” John A. Scarlett, MD, chairman and chief executive officer of Geron, said in the press release.

Investigators of the double-blind, placebo-controlled, phase 3 Imerge study evaluated imetelstat compared with placebo among patients with low or intermediate-1 risk, transfusion dependent MDS who have not received prior treatment with either a hypomethylating agent or lenalidomide (Revlimid). A total of 178 patients were randomly assigned 2:1 to either receive 7.5 mg/kg of imetelstat intravenously every 4 weeks (n = 118) or matched placebo (n = 60). Study treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or lack of response.

Key secondary end points of the trial included time to 8-week red blood cell infusion, duration of TI, and the rate of hematologic improvement erythroid defined as a rise in hemoglobin of 1.5 g/dL or more above pretreatment levels for 8 weeks or a reduction of 4 or more red blood cell transfusions over 8 weeks.

Patients 18 years and older with a diagnosis of MDS per World Health Organization guidelines confirmed by bone marrow aspirate and biopsy within 12 weeks prior to beginning treatment were eligible to enroll on the study. Additional inclusion criteria included being red blood cell transfusion dependent and having an ECOG performance status of 0 to 2.

Trial investigators reported statistically significant improvements in 8-week TI with imetelstat vs placebo across lower risk MDS subtypes. The 8-week TI was 45.2% vs 18.9% (P = .016) for patients with ring sideroblast-positive MDS and 31.8% vs 8.7% (P = .038) for patients who were negative in the imetelstat and placebo cohorts, respectively.

The 8-week TI was 45.2% vs 21.2% (P = .027) for patients with a transfusion burden of 4 to 6 units and 33.9% vs 7.4% (P = .023) for patients with more than 6 units in the imetelstat and placebo arms, respectively. In terms of International Prognostic Scoring System risk categories, the 8-week TI was 40.0% vs 20.5% (P = .034) for patients with low-risk MDS and 39.5% vs 4.8% (P = .004) for those with intermediate-1 MDS in each respective cohort.

Trial investigators highlighted that safety results were consistent with previously reported findings for imetelstat in a clinical setting. Treatment discontinuation was observed among 77.1% and 76.3% of patients in the imetelstat and placebo cohorts, respectively.

The most frequently observed treatment-emergent adverse effects (TEAEs) in the imetelstat cohort included asthenia, COVID-19, peripheral edema, headache, diarrhea, and alanine aminotransferase increase. The most common hematologic TEAEs included grade 3 or 4 thrombocytopenia in 61.9% vs 8.5% of patients and neutropenia in 67.8% vs 3.4% of patients in the imetelstat and placebo cohorts, respectively.


Geron announces positive top-line results from IMerge phase 3 trial of imetelstat in lower risk MDS. News release. Geron. January 4, 2023. Accessed January 6, 2023.

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