MPN Workshop of the Carolinas 2025 | Promising combination strategies being explored in myelofibrosis

I’m quite excited to see the results with the XPORT, the selinexor and ruxolitinib are going to show, because the first results or the preliminary or kind of like more mature data of the spleen responses were robust. So I really want to see and get that feeling. That could be with the symptoms as well, because those are very kind of hot. So I think that is very important. It is very important molecule that has a needed and important role in oncology in general with the transport of these different molecules, so it is kind of expected to have a big role it’s already improved across different indications. So we will have to see how we can use it for our patient not only for the spleen and symptoms, but more for a deeper dive in responses or what have we really done with the disease so far with adding on a new molecule. 

Then the MDM2 inhibitor that is a kind of a hot topic. I think more importantly there is the design of the study using the navtemadlin-ruxolitinib or ruxolitinib-placebo in a frontline but semi-frontline patient that would be suboptimal with single agent ruxolitinib. I think that is a very important design that will hopefully finally answer all the questions: what do we add into patients outcomes adding a second drug when we add it to the patient that need it. So we have a lot of patients in our population that would say I don’t want to take two drugs up front maybe because it’s just more toxicity my disease doesn’t seem to be so bad, which is a valid point, but at the same time we know that with a single agent we don’t stop the disease from progressing, So what is this add-on approach adding is to stop that or halt that or slow it down. So that is something that we were not even able to look at because we haven’t had the endpoints, we haven’t even been thinking behind that. So this design is very unique and very important to have in the space to really assess in a prospective, very well designed fashion, what does it actually do, what does it actually add. I think the molecule is very exciting and has excellent data across all phases clinical trials including grade 8 and refractory setting, so what it’s going to bring to frontline aka sub-optimal ruxolitinib patients it’s going to be really really important to learn. 

So I consider those two because of the latest development to be very important but I actually very like the newer molecules that come in a space that address the refractory patients that really could show us how do we impact the information behind, for example the PIM kinase molecule and others, that really could answer a lot of these cytokines release, does it correlate with outcome questions, which hopefully will help us to bring the field forward to get the movements more and to not only think do we add more molecules, but more which ones to which patients. I think those are really the most exciting. There’s a lot of excitement. I think the calreticulin, again, will be moving in a space. We’ll be soon talking about more combinations with just one. But I think to really learn where do we put it and how do we assess it so people benefit and are we able to develop a design that’s going to really stop the disease from progressing, it’s really the most important.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.