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EBMT 2023 | Approved & emerging JAK inhibitors for patients with high-risk MF who are transplant-ineligible

Jean-Jacques Kiladjian, MD, PhD, Saint-Louis Hospital & Paris Diderot University, Paris, France, outlines treatment options for patients with high-risk myelofibrosis (MF) ineligible for allogeneic stem cell transplantation (alloSCT). Whilst the two currently approved JAK inhibitors in Europe, ruxolitinib and fedratinib are useful to manage constitutional symptoms and splenomegaly, they are also associated with cytopenia. Two recently developed JAK inhibitors, momelotinib and pacritinib, help improve both anemia and symptoms, and their approval in Europe is eagerly awaited. This interview took place at the 49th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) held in Paris, France.

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Transcript (edited for clarity)

So, for patients at high risk who are not eligible for transplantation, we have now several drugs that help us to take care of them. We have of course, the JAK inhibitors, currently in Europe, two of them are approved and available commercially. Ruxolitinib, of course, that we know for more than ten years now and more recently, fedratinib. So, we have these two drugs that help us to manage patients, especially take care of symptoms, constitutional symptoms, and splenomegaly...

So, for patients at high risk who are not eligible for transplantation, we have now several drugs that help us to take care of them. We have of course, the JAK inhibitors, currently in Europe, two of them are approved and available commercially. Ruxolitinib, of course, that we know for more than ten years now and more recently, fedratinib. So, we have these two drugs that help us to manage patients, especially take care of symptoms, constitutional symptoms, and splenomegaly. However, we also have some problems with patients with cytopenia because of course these two JAK inhibitors inhibit JAK2, which is necessary to produce red cells and platelets. And often when you start treatment with one of these drugs, you will decrease the level of hemoglobin, the level of platelets in our patients, worsen anemia for those who are already anemic starting the drug, so we have some still unmet needs for these patients. More in the near future, we hope that we will have two other JAK inhibitors that may help us to manage these cytopenic patients. One of them is Pacritinib, already approved in the United States but not yet in Europe, and the other is more momelotinib that has been shown in a recent study called MOMENTUM to induce interesting results in terms of symptoms and transfusion independency in patients who are anemic. So the interest of these two new JAK inhibitors is that in addition to JAK2, they target also another receptor ACVR1, which is a receptor on the hepatocyte that plays a role in the metabolism of iron through the hepcidin and blocking ACVR1 induces a reduction in hepcidin level and then an iron available for erythropoiesis and improvement of anemia. Indeed, pacritinib and momelotinib have this target in addition to JAK2 and could be nice treatments for patients with cytopenia.

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