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EHA 2026 | Exciting advances in the MPN field: novel JAK inhibitors, targeting mutant CALR & more
Naveen Pemmaraju, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, gives an overview of exciting advances in myeloproliferative neoplasms (MPNs), including the development of novel JAK inhibitors, CALR-targeting approaches, and the emerging hepcidin mimetics and modulators. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
I’m really excited for research on behalf of our patients in the MPNs field. I believe we’re entering into a second golden era now, post-JAK inhibitors. And I’d like to highlight three areas that are being really robustly mentioned here at EHA. The first area is that of targeting the mutant JAK specifically. So with the ruxolitinib and the four approved JAK inhibitors, those are what we call type 1 JAK inhibitors, and they hit the JAK-STAT pathway...
I’m really excited for research on behalf of our patients in the MPNs field. I believe we’re entering into a second golden era now, post-JAK inhibitors. And I’d like to highlight three areas that are being really robustly mentioned here at EHA. The first area is that of targeting the mutant JAK specifically. So with the ruxolitinib and the four approved JAK inhibitors, those are what we call type 1 JAK inhibitors, and they hit the JAK-STAT pathway. But now we’re entering into this new era of can we target the mutation selectively or specifically? And so we’re hearing data about that approach for the first time in patients in phase 1 dose escalation. So I’d like us to follow that field closely and all the different ways of targeting the mutant JAK. The second exciting area is that of targeting mutant CALR. So following this theme in MPNs, where we used to have a more mutation-agnostic approach, now we’re trying to target the two big drivers. So JAK2, as I mentioned, but also CALR. So let’s keep our eye on that, both preclinical data and as these enter into the field. The one unique aspect of CALR that I’d like to highlight for the audience is that it may have immune properties. And so that may allow it to be approached by CAR-T cells in the future, bispecifics, monoclonal antibodies. So the two are quite different mutations, aren’t they? The JAK2 and CALR, and it’s opening up this new era of therapeutics. Still, a third and final area I’d like to highlight is that in polycythemia vera of the hepcidin mimetics and modulators, this is a brand new class of drugs that we hope to see soon. Hepcidin is the master regulator of iron homeostasis in the body. And so in polycythemia vera, elevated hematocrit, these type of drugs aim to restore that homeostatic balance. So I’m excited to see that data. The latest compound in that investigational area has been that of rusfertide. So we’re seeing updated results on that and still many other drugs in that class in phase one to phase three.
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