Abstract
Imetelstat is a first-in-class, direct, and competitive inhibitor of telomerase enzymatic activity that selectively induces apoptosis of malignant clones and allows for recovery of erythropoiesis. Imetelstat was approved by the United States Food and Drug Administration in June 2024 and the European Medicines Agency in March 2025 for the treatment of certain patients with lower-risk (low to intermediate-1) myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia who have failed or lost response to or are ineligible for erythropoiesis-stimulating agents. Imetelstat is infused at 7.1 mg/kg (active dose, equivalent to 7.5 mg/kg sodium salt) intravenously over 2 hours once every 4 weeks. In the pivotal IMerge trial in LR-MDS, significantly more patients treated with imetelstat vs. placebo, respectively, achieved ≥ 8-week RBC-transfusion independence (TI; 40% [95% confidence interval [CI] = 30.9-49.3] vs. 15% [95% CI = 7.1-26.6]) and ≥ 24-week RBC-TI (28% [95% CI = 20.1-37.0] vs. 3% [95% CI = 0.4-11.5]). The safety profile of imetelstat was characterized primarily by cytopenias, including neutropenia (incidence of 74% any grade and 68% grade 3-4 events) and thrombocytopenia (75% and 62%, respectively). Grade 3 to 4 hematologic events occurred early in the treatment and had a median duration of 1.9 weeks for neutropenia and 1.4 weeks for thrombocytopenia; cases resolved to grade ≤ 2 within 2 weeks in 81% and 86% of cases, respectively, with limited severe complications. This review highlights key topics related to the use of imetelstat in patients with LR-MDS, including its mechanism of action, clinical efficacy and safety data, dosing and administration, management of adverse events, and notable clinical practice implications.