What are some effective ways to manage anemia in myelofibrosis?

What are some effective ways to manage anemia in myelofibrosis? Anemia is a complex one because it's a multifactorial, driven aspect of the disease. It could be poor blood cell production. It could be destruction bone. It could be splenic sequestration. It it could be blood loss from from esophageal varices. So there's a lot of different reasons why people can have anemia with myelofibrosis.

So the important thing is to try to understand in that given individual what mechanisms you think are driving the anemia, is it blood loss and they need iron. Is it B12 deficiency? Those are kind of easy ones. Or is it problems with what's called hepcidin, which is a inflammatory marker that mediates iron availability for erythropoiesis.

So you could use hepcidin and directed therapies. Or is it poor production and you need to stimulate the bone marrow with growth factors. So there's a lot of interest today in trying to understand, which mechanism. And like most things that I'm it's never one thing. It's probably multiple mechanisms that are different in every given individual. And it's, it's nice to even imagine that in 2025, we even have Jak inhibitors that we have available to us that can offset anemia and improve anemia in some patients, like momelotinib and pacritinib which are ACVR-1 inhibitors.

So we're moving into an area where there is a lot of focus on alleviating anemia. As we understand the mechanisms that drive anemia, we are able to develop more effective therapies. But the therapies that a lot of patients may be already familiar with are drugs like procrit and aranesp, Those are the erythropoiesis-stimulating agents, or a drug that will likely hit the market for myelofibrosis and is available for MDS, which is a drug called luspatercept, which is an erythropoiesis-maturation agent.

And then historically we've used drugs like danazol, a synthetic androgen or even immunomodulatory drugs like thalidomide or lenalidomide or pomalidomide to address anemia? But if I were just to sum it up, all of those drugs sort of somewhere around 20 to 30% response rate for anemia, and sometimes that's improvement in hemoglobin. That's sometimes getting patients out of the transfusion suite.

But often the problem is those responses aren't durable. And that's why we really need better therapies.