Imetelstat Shows Promising Results for Lower-Risk MDS in a Phase 2 Trial
Dr. Rami Komrokji, Vice Chair of the Malignant Hematology Program, is a joint senior author on a very high-impact paper titled: “Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebocontrolled,phase 3 trial" recently published in The Lancet.
Background: Unmet medical needs remain in patients with red blood cell transfusion-dependent (RBC-TD) lower-risk myelodysplastic syndromes (LR-MDS) who are not responding to or are ineligible for erythropoiesis-stimulating agents (ESAs). Imetelstat, a competitive telomerase inhibitor, showed promising results in a phase 2 trial.
Methods: In phase 3 of IMerge, a double-blind, placebo-controlled patients (aged ≥18 years) with ESA-relapsed, ESA-refractory, or ESA-ineligible LR-MDS (low or intermediate-1 risk disease as per International Prognostic Scoring System [IPSS] criteria) were randomly assigned (2:1) to receive imetelstat 7·5 mg/kg or placebo.
Results: 178 patients were enrolled and randomly assigned (118 to imetelstat and 60 to placebo). In the imetelstat group, 47 (40% [95% CI 30·9-49·3]) patients had an RBC-TI of at least 8 weeks versus nine (15% [7·1-26·6]) in the placebo group (rate difference 25% [9·9 to 36·9]; p=0·0008). Overall, 107 (91%) of 118 patients receiving imetelstat and 28 (47%) of 59 patients receiving placebo had grade 3-4 treatment-emergent adverse events. The most common treatment-emergent grade 3-4 adverse events in patients taking imetelstat were neutropenia (80 [68%] patients who received imetelstat vs two [3%] who received placebo) and thrombocytopenia (73 [62%] vs five [8%]). No treatment-related deaths were reported.
The study demonstrated clinically meaningful benefit with Imetlestat for MDS patients with durable red blood cell transfusion independency among different subtypes of lower risk MDS especially among those patients with high transfusion need. The correlative studies also suggest potential disease modifying effect. Approval of this treatment will hopefully offer our patients a new option for MDS treatment.
Dr. Rami Komrokji
UPDATE: Dr. Komrokji was part of a team who successfully presented this data to ODAC FDA in March 2024 where ODAC committee members voted 12/2 in favor of drug approval and it is expected that FDA will grant approval by June 2024.
Open Clinical Trials for MDS:
- The National Myelodysplastic Syndromes (MDS) Study
- A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients with Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK)-Inhibitor
- Phase 2, Single Arm Study of Luspatercept for the Treatment of Anemia in lower Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Myelodysplastic Syndromes/Myeloproliferative Neoplasms (MDS/MPN)
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