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ASH 2025 | Correlation between IL-8 and TNF-alpha levels and OS in patients with R/R MF treated with imetelstat
Prithviraj Bose, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the Phase II IMbark trial (NCT02426086), which investigates two doses of the telomerase inhibitor imetelstat in patients with myelofibrosis (MF) who are relapsed/refractory (R/R) to a JAK inhibitor. Dr Bose notes that the study demonstrates a survival benefit with the higher dose of imetelstat, as well as down-regulation of cytokines such as interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha, which correlated with improved overall survival (OS). This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
IMbark is a very important phase 2 trial that was done of Imetelstat, which is a telomerase inhibitor, already approved for myelodysplastic syndromes with lower risk disease and anemia, which is being investigated in myelofibrosis. In fact, they have completed accrual to a large phase 3 study called the IMpactMF trial, which has overall survival as its primary endpoint...
IMbark is a very important phase 2 trial that was done of Imetelstat, which is a telomerase inhibitor, already approved for myelodysplastic syndromes with lower risk disease and anemia, which is being investigated in myelofibrosis. In fact, they have completed accrual to a large phase 3 study called the IMpactMF trial, which has overall survival as its primary endpoint. These are patients who have failed JAK inhibitor therapy. However, what we are discussing today is IMbark, which is a phase 2 already published, and this looked at two different doses of Imetelstat. One was the 9.4, which is believed to be the active dose, milligram per kilogram every three weeks IV. The other was half of it, 4.7.
Now, we already know from what’s been published from IMbark that there was an apparent survival benefit for the patients who got the 9.4, the higher dose. Their median survival, and remember this is JAK inhibitor failure, so both Imbark and IMpactMF are in the second line JAK inhibitor exposed failed setting. Now, given that, the median survival of about 28 months was about double of what has historically been reported about 13 to 14 months in this setting.
Now what this poster adds at this ASH meeting is that it really correlates some cytokines which we well recognize as being pathophysiologically important in myelofibrosis like IL-8, TNF-alpha, it shows us the down-regulation of these cytokines. We already knew that Imetelstat is able to improve bone marrow fibrosis and reduce the driver mutation allele burden, but it’s new, this data is new showing that it can reduce these important cytokine levels, IL-8, TNF-alpha, and that had a correlation to that survival benefit that I just mentioned.
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