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General Updates | An update on imetelstat in R/R myelofibrosis

Jean-Jacques Kiladjian, MD, PhD, Saint-Louis Hospital & Paris Diderot University, Paris, France, gives an update on the use of imetelstat in relapsed/refractory (R/R) myelofibrosis (MF). The results of the Phase II IMbark trial (NCT02426086) led to ongoing Phase III IMpactMF trial (NCT04576156) which is currently assessing the efficacy of this agent in patients with high-risk disease who are resistant to ruxolitinib, with overall survival (OS) as its primary endpoint. This interview took place virtually.

Transcript (edited for clarity)

Imetelstat is a telomerase inhibitor that has been developed for many years in solid tumors with disappointing results, and, where it was found to have a nice activity, in myeloid malignancies, with two first preliminary studies in small cohorts of patients with ET and myelofibrosis that led indeed to the development of imetelstat in patients with myelofibrosis. The Phase II trial showed that indeed the patients with the poorest prognosis, meaning, for example, those who are so-called triple-negative for the driver mutations, had indeed a quite better than expected survival with imetelstat...

Imetelstat is a telomerase inhibitor that has been developed for many years in solid tumors with disappointing results, and, where it was found to have a nice activity, in myeloid malignancies, with two first preliminary studies in small cohorts of patients with ET and myelofibrosis that led indeed to the development of imetelstat in patients with myelofibrosis. The Phase II trial showed that indeed the patients with the poorest prognosis, meaning, for example, those who are so-called triple-negative for the driver mutations, had indeed a quite better than expected survival with imetelstat. So this prompted the start of a Phase III trial that is ongoing, the so-called IMpactMF study, that indeed tests imetelstat in patients with myelofibrosis refractory or resistant to ruxolitinib, but with a very strong primary endpoint for the first time in these diseases in the recent years, that is overall survival. So the bar is high. We expect that we may improve the overall survival of patients with the worst-prognosis myelofibrosis with this drug. That obviously will not be a first-line drug, because it’s quite complicated to use; it’s intravenously administered, you have to be careful with some complications, but could be a real new alternative for the patients who are escaping to JAK inhibitors and have a worse prognosis.

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Disclosures

Advisory boards for Novartis, Abbvie, BMS, AOP Orphan.