ASH 2024 | An update of IMproveMF: dose-escalation of imetelstat + ruxolitinib in patients with myelofibrosis

We got to present really preliminary data from the IMproveMF trial, and I think this is certainly a trial and an idea, a concept that I’m very excited about, very intrigued by, and I think many are, right? Because I think certainly we know two things. We know that we’re not in a position where we’re going to get away from JAK inhibitors at all from the treatment of myelofibrosis, JAK inhibitors are really quite critical. Certainly we can discuss which is the right JAK inhibitor to use at the right time, but myelofibrosis is a disease that’s hallmarked by JAK/STAT activation and patients by and large benefit greatly from using JAK inhibitors. That being said, JAK inhibitors don’t do enough, right? They don’t get rid of the underlying disease. They don’t lead to meaningful remissions. They lack durable therapy in many cases. And so I think that we can do more. 

What we learned from the kind of development of imetelstat in the Phase II setting in myelofibrosis is that patients on the higher dose of imetelstat actually lived longer than we would have expected and lived longer than the patients that were on the lower doses. And so, that combined with some preclinical translational data that suggests that imetelstat may specifically target the malignant hematopoietic stem cell and have some disease-modifying characteristics. I think it was a natural combination to study the ruxolitinib in combination with imetelstat to see if you can get those kind of symptomatic spleen reduction, anti-inflammatory benefits that come with ruxolitinib and combine that with potential disease-modifying impacts of imetelstat. Question being, if you do that, can you improve how patients feel and improve their overall survival and outcomes? Can you delay progression of the disease? Can you create meaningful remissions of the disease? Can you create more durability of response to it with ruxolitinib. 

And I think what we presented was really early phase data. So we’re still in the dose escalation phase that was presented looking at four different dose levels. And fortunately, we saw that these agents can be combined without significant toxicity, so no DLTs. We were able to kind of escalate to the highest planned dose. And now we’re entering into this expansion phase where we’re now going to test that higher dose in combination with ruxolitinib, actually starting with enrollment of patients prior to them actually going on ruxolitinib. So now I think we’ll get to see kind of the interesting efficacy data and durability data as we start to really expand this trial outward. So, you know, really early data, but very encouraging in terms of these agents can be safely combined, didn’t see anything that limited us going up to the higher dose, and now we’ll expand that out and really see how this performs.

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