EHA 2025 | Recent advances and trial updates in MPNs: insights from EHA 2025

This is a very happening EHA for MPN. So we have a plenary presentation by Dr Harry Gill on the SURPASS ET study. This was a pivotal trial of ropeginterferon alfa 2b versus anagrelide in patients with hydroxyurea-resistant or intolerant ET. And this was, this accrued mostly in China. However, you know, it is a pivotal trial. We had this open too at our institution. I’ve enrolled patients on it. We know the top-line results, you know, as we await the actual presentation, which show that ropeginterferon alfa 2B was significantly superior for a durable, complete hematologic response at nine months and 12 months. So that was very much in favor of Ropeg and as were all the other endpoints. So this is clearly something to watch. There is also the late-breaker session on Sunday where John Mascarenhas will be presenting the first results of the Insight monoclonal antibody against mutant CALR. So we know that mutant CALR drives about 20 to 30 percent of both MF and ET. And what’s nice about mutant CALR is because of the mutation, the protein, which is basically an endoplasmic reticulum chaperone protein, comes out to the cell surface. So this is because of the mutation. So wild-type CALR will not do this. But because it comes out, it becomes amenable to immunologic targeting. So this is a naked monoclonal antibody approach against this, you know, the mutant CALR, which is on the cell surface. And obviously a very, very exciting approach because you’re really getting to the driver of the disease. And this is the results at EHA are for the ET cohort where there’s been some nice responses seen. Now, those two, of course are going to, they’ll have the spotlight on them because they were plenary and late-breaker, but there are also several other important abstracts being presented in the oral sessions, for example. One is the 72-week follow-up of MANIFEST II, the Phase III trial of ruxolitinib and pelabresib versus ruxolitinib and placebo in JAK inhibitor-naive patients with myelofibrosis. Alessandro Vannucchi is going to present that. The 72-week data show that the superiority of pelabresib and ruxolitinib is maintained over ruxolitinib and placebo. And you still see those same trends that you saw at the 24-week. So spleen response is much higher. Symptom response about the same, not much of a difference. Anemia response is better for the pelabresib arm. Importantly, the proportion of patients who have a dual spleen and symptom response still much better for the pelabresib and ruxolitinib. So really everything that we saw at 24 weeks pretty much maintained at 72 weeks and very importantly there was a concern about leukemic transformation which was you know numerically higher at 24 weeks in the pelabresib arm. What is nice to see now is that although it is still higher, that delta is coming down. So the difference between the two arms with greater follow-up is absolutely narrowing which is very very reassuring. Other abstracts, elritercept, very exciting. This is an active in receptor ligand trap. So in general in the same family as sotatercept, luspatercept, but definitely with a difference targeting the active in receptor A more than the B. And this drug, you know, we’ve had a few presentations. Of course, it is meant for anemia, but we’ve seen some intriguing spleen and symptom responses as well. So, Claire Harrison presenting an update on this. And then we have novicertib. Novicertib is the PIM1 kinase inhibitor from Sumitomo. Again, we’ve been hearing about this about, 77 or so patients that have been reported on receiving the monotherapy. So this again is an update on the monotherapy. Excitingly, this drug in myelofibrosis is being combined with ruxolitinib in the add-on setting as well as with momelotinib in patients who’ve had another JAK inhibitor. So starting with momelotinib and novicertib in those patients, those results are not at EHA. This is monotherapy, we’ve seen clear activity, particularly for symptoms more than spleen although there’s been some spleen responses as well and the symptoms nicely correlating with cytokine reduction. So those are some of the newer drugs you know the pelabresib you know not so new anymore but the pelabresib update, novicertib, elritercept. I will mention that Ropeg again coming back to Ropeg of course there’s the plenary session presentation that we talked about on ET and Surpass ET but there’s also an oral session presentation also by Harry Gill on early myelofibrosis. Now this is an area of unmet need. In early MF you often don’t have an indication for a JAK inhibitor at least conventionally the way we think about it and there you know you still want something disease-modifying. So this is an important study being conducted mostly in Asia of Ropeginterferon alfa 2b in early MF so early overt MF or pathologically defined pre-fibrotic MF. So it’s really in both of those settings. So we’ll hear an update on that. And finally, I’ll finish with one important practically useful abstract from the JUMP trial. So folks will recall that JUMP was this large Phase IIIB, 2000 plus patient trial of ruxolitinib in myelofibrosis years ago, been published a couple of times. However, this abstract presented at an oral session by Pankit Vachani shows that you can actually fairly effectively counteract the ruxolitinib-induced anemia with the agents we currently have. So, ESAs, danazole, not even luspatercept because when this trial was done, there was really not much luspatercept used in those settings, although we use it very much in the US, it’s NCCN endorsed, etc. But again, this abstract showing that it is very possible to maintain an effective dose of ruxolitinib and thwart a lot of the anemia that it causes using conventional agents such as ESAs and danazole.

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