SOHO 2026 | Individualizing JAK inhibitor selection in myelofibrosis: which agent for which patient?

Yeah, this is a nuanced and complicated topic, but I’ll do my best in just a few minutes here. So I think, you know, ruxolitinib has been around for 15 years. It is undoubtedly a great drug in terms of what it can do for spleen and symptoms. It improves survival. But I think what is important to understand that this is a dose-dependent drug. So yes, it has some great benefits, but those are really best achieved when you can give it at a high dose at 20 twice a day, ideally, maybe 15 twice a day, but probably not lower. Okay. So I think, you know, we need to recognize that ruxolitinib is excellent for a lot of people, but not perhaps the best for patients with, you know, cytopenic phenotypes where their counts are low and you’re giving them a low or suboptimal dose of ruxolitinib, right? And that’s where I think momelotinib and pacritinib come in. They both have anemia benefits. I think anemia benefits are greater for momelotinib, but pacritinib is a very helpful drug because you can use it regardless of platelet count. So it is a very nice tool to have in those settings. Although for anemia per se, I think momelotinib is a better drug. Now, both with momelotinib and pacritinib, we have data sets to show that when you’re comparing them to low-dose drugs, you know, you really can maintain the dose intensity way better with momelotinib, pacritinib. You know, what I mean to say is that in a cytopenic setting, you have to really reduce rux a lot. And then are you really getting the benefit? So I think that’s very important. Momelotinib in the front line is increasingly something we are thinking about. And, you know, they actually have non-inferiority data to rux for spleen. So that’s important. And they have obviously the anemia benefits. So I think for an anemic frontline patient, it’s a very reasonable option, you know. So that has expanded our options a bit in the frontline as well. Pacritinib, of course, for very low platelets usually is where we go with that, although they have data up to platelets of 100. So it’s not like they’re not truly restricted to just less than 50, although that’s the label. So I think, you know, those are the three most used drugs. But I will put in a plug for fedratinib just to say that in the second line after ruxolitinib, if the counts are still preserved, let’s say big spleen, some symptoms, but the counts are still preserved, then I think that is actually perhaps the way to go. It is not used very much because, you know, as people progress on ruxolitinib, usually the counts go down. And so there’s not much of a role left for fedratinib there. And you’re looking at momelotinib or pacritinib. But I think fedratinib is a very decent drug in the second line when the patient still has a proliferative phenotype rather than very cytopenic. So I think, you know, they all have their place and the survival benefit of rux is maybe a class effect. You know, it may not be just that rux has it. You know, they were able to compare themselves to placebo. So they were the first drug. I mean, so some of it is that, but also, and, you know, at least with pacritinib and fedratinib there were clinical hold issues that prevented them from doing long-term analyses, there are all those things, so I think it’s important to know who to use it in and when, which is really the spirit of your question. I think those are some highlights, but this can be a very nuanced topic.

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