Ruben Mesa, MD: Let’s pivot toward myelofibrosis [MF]. We’re going to take a deep dive into myelofibrosis. The first aspect is to understand, setting the stage in terms of diagnosis, prognosis, and treatment goals before we start talking regarding the therapies. Angela, why don’t you start us out as it relates to the diagnosis of myelofibrosis. What does that look like in this modern era?

Angela Fleischman, MD, PhD: In terms of myelofibrosis, it’s important to note that it’s not just fibrosis in the marrow. A lot of times patients think fibrosis in the marrow equals the disease we call myelofibrosis, although people with myelofibrosis obviously have fibrosis in the marrow. It’s much more complicated than that because people with PV [polycythemia vera] or ET [essential thrombocythemia] can have some fibrosis in their marrow, as well as other things like autoimmune diseases that can cause fibrosis in the marrow.

A key feature of myelofibrosis vs PV or ET is the appearance of the megakaryocytes, their dysplastic appearance, and the designation of this prefibrotic myelofibrosis. But with a diagnosis of myelofibrosis, it’s quite different from carrying a diagnosis of PV or ET because the prognostic consequences are much different from somebody with PV or ET. It’s a much more serious diagnosis to carry. With myelofibrosis, unfortunately, a lot of people can have cytopenia.

I want to clarify that each myelofibrosis in my mind is unique. Each person has their unique features and problems. A lot of people have cytopenia, and that may be how they first present. In particular, somebody who presents with primary myelofibrosis, a lot of times it will be discovered in the context of a work-up for anemia.

Ruben Mesa, MD: That’s a great overview. Sometimes there’s this issue of early myelofibrosis vs more traditional myelofibrosis. Some people get trapped up on this. I share with our trainees and my cancer center that early MF frequently looks a lot like ET and is managed a bit like ET. We need to be mindful of it, but how do you separate those 2 things in your mind?

Angela Fleischman, MD, PhD: In my mind, a lot of times myelofibrosis patients can be proliferative. But if, say, an ET person has some anemia, I’d be a little concerned that they really have a myelofibrosis. You can use clues: is their spleen very enlarged? Are they extremely fatigued? Is their symptom profile much more extreme than you would expect from an ET person? Is their LDH [lactate dehydrogenase] elevated? Those things can help when looking at a patient, help you increase your suspicion for myelofibrosis over ET.

This transcript has been edited for clarity.