ASH 2024 | The post-approval utilization of pacritinib and momelotinib in myelofibrosis

So, I think when we look at kind of the new age of JAK inhibitors, we have four that are now approved, ruxolitinib, fedratinib, pacritinib, and momelotinib. Many of these have distinguishing factors, right? Ruxolitinib first in class, first approved, very tolerable, tends to cause anemia and thrombocytopenia, but certainly improves spleen and symptoms. Fedratinib, second approved, certainly a potent JAK inhibitor, a little bit of a more difficult toxicity profile, still causes anemia, thrombocytopenia may have a niche in the 50 to 100,000 platelet group. But pacritinib and momelotinib are the most recently approved, and I think they really have overlapping efficacy profiles. Certainly, pacritinib is approved on an accelerated basis for patients with marked thrombocytopenia. Momelotinib is approved for myelofibrosis and anemia. That being said, momelotinib has been used in patients that have low platelets. Pacritinib inhibits ACVR1 and may help with anemia. And so really, these are agents that I think beyond their labels, we can certainly look at using in very similar patient populations. And I think that we’re going to need more education as we go forward to know exactly when to leverage these agents. 

Unfortunately, we’re not going to see a head-to-head trial prospectively. So I think it’s on us as investigators to go back and try to gather this data and look at our current use of these agents in the real world to, one, see, okay, who’s receiving these in the real world? Is it different patient populations? And then, two, start to look at outcomes as far as how they perform. But I don’t think we can just look at outcomes and how they perform because very, very likely they’re being used in very different patient populations, which are going to impact the outcomes that we see. 

And so, you know, I think this was our first look at around 50 patients that have been treated since their approvals of both pacritinib and momelotinib in the real world. What we saw was not overly surprising, right? Both of those agents had the ability to improve hemoglobin counts. That improvement in hemoglobin was seen more likely in patients that were switching from ruxolitinib over to these newer agents, which is certainly, I think, what we’re seeing in practice. We saw that the durability of treatment was longer with momelotinib. Patients were really only on pacritinib for a short period of time. And I think that speaks less to the specific agents and more to the fact that pacritinib is often used in patients that have really kind of refractory advanced disease that have very low platelets and so they don’t end up staying on treatment for a very long time. And I think as we get more patients in this cohort, we can start to kind of tease out the true impact in similar patient populations. But again, that’s going to be research that will be presented at a later date.

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