ASH 2024 | The biggest MPN updates from ASH 2024

So there’s of course a lot of trials each year at ASH and you know we can certainly discuss those but I would maybe start by a few of the things that caught my attention regarding things that one can do today or that inform practice today. So for example you know there was a presentation from Europe, Claire Harrison and others in her group about CALR VAF dynamics. So as you treat ET patients with ruxolitinib or interferon or anagrelide or hydroxyurea, what happens to the CALR variant allele frequency? And somewhat expectedly, we saw that with ruxolitinib and interferon, it goes down, whereas with anagrelide and hydroxyurea, it goes up. Of course, it is not surprising and actually sort of indicates what we think. But something provocative that was brought up was that we’ve known, for example, that anagrelide can cause an increase in bone marrow fibrosis. And what is intriguing is could that be because it’s increasing CALR VAF? We know that CALR is one of the mutations that does increase propensity to developing bone marrow fibrosis. So I found that actually very intriguing. Now a brief mention of fedratinib which is a commercially available agent. There were two presentations one from Andrew Kuykendall of Moffitt from an investigator-sponsored trial in MDS-MPN overlap. So it’s really nice to see something being done in that space which really doesn’t have a clear standard of care and clearly fedratinib is an active agent. And then also from the FREEDOM2 study which is post-ruxolitinib myelofibrosis patients, already published in the Lancet Hematology by Claire Harrison and others. But in the oral presentation at this meeting from Dr Al-Ali, the focus was on low platelet patients, those between 50 and 99,000 baseline platelets, and really goes to show that fedratinib absolutely preserves its efficacy in this group of patients. It might even be better than in patients with 100 and higher platelets. Normally, you assume that the lower platelets are the harder ones to treat. And that is a fact. But here, somewhat refreshingly and surprisingly, you’re seeing as good and perhaps better responses with fedratinib for spleen, for example, in this lower platelet subgroup. Now, this does agree with what we already knew from JAKARTA. But the FREEDOM trials have, you know, the FREEDOM2 trial specifically has a much larger sample size. And then I’ll just quickly mention that there was a very interesting presentation by Francesca Palandri from Italy on really looking at maybe if we should rethink, I think we all agree that we should rethink the risk stratification of polycythemia vera. And so they were looking at a number of factors that may inform our decision making and risk stratification beyond the usual age and prior thrombosis which we have known for a long time. And I’ll conclude by saying there was also a very interesting presentation on pulmonary hypertension in myelofibrosis which we all know happens and it can be a difficult problem for our patients. This particular study that I really noted was that the pulmonary hypertension can actually also correlate with hematologic progression beyond cardiovascular complications which obviously are going to happen but also correlated with hematologic progression just drawing more attention to what is a difficult problem in our patients.

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