Targeting Telomerase in Low-Risk MDS: The Role of Imetelstat

Imetelstat represents a novel, disease-modifying approach for patients with lower-risk myelodysplastic syndromes who have limited options after standard therapies. Its mechanism of action centers on the inhibition of telomerase, an enzyme that enables malignant hematopoietic progenitor cells to maintain telomere length and continue unchecked proliferation. By targeting telomerase, imetelstat preferentially affects the clonal cells driving MDS while allowing normal hematopoiesis to recover. The phase 3 IMerge trial was pivotal in demonstrating clinically meaningful and durable transfusion independence in heavily pretreated, transfusion-dependent patients, supporting its FDA approval. Optimal candidates for imetelstat include patients with lower-risk MDS who are refractory to or ineligible for ESAs and other agents such as luspatercept, particularly those with significant transfusion burden. Its introduction marks an important shift toward therapies that address underlying disease biology rather than solely managing symptoms.