Imetelstat in myeloid malignancies: current data and future directions

Telomerase reactivation allows cancer cells to maintain telomere length and evade senescence, making it an appealing therapeutic target. Imetelstat, an antisense oligonucleotide, is the first clinically effective telomerase inhibitor approved by the FDA and the European Commission for treating anemia in transfusion-dependent low-risk myelodysplastic syndromes (MDS).

Sources for this review were identified through searches of PubMed, ClinicalTrials.gov, and conference abstracts. This review highlights the pharmacology, efficacy, and ongoing trials of imetelstat in treating MDS, myelofibrosis, essential thrombocythemia, and other malignancies. In the IMerge trial, imetelstat induced durable transfusion independence in heavily transfused LR-MDS patients. Pilot trials in myelofibrosis suggest imetelstat's potential disease-modifying properties and survival benefit, warranting further studies of imetelstat as a monotherapy or in combination therapies. Imetelstat can cause thrombocytopenia, leukopenia, elevated liver enzymes, and infusion reactions, which are mostly reversible but may rarely lead to fatal events.

Future clinical trials in LR-MDS should focus on optimal sequencing and combination strategies for imetelstat with other agents, and identifying biomarkers that can predict response. Monitoring real-world outcomes will offer valuable insights into imetelstat's safety and efficacy in patient populations underrepresented in clinical trials. Imetelstat's role in other malignancies, especially myelofibrosis, is being explored.