Myelofibrosis Treatment Approaches after Disease Progression


A look at the potential treatment options for a patient with myelofibrosis who progresses after first-line therapy.

Rami Komrokji, MD: This patient got ruxolitinib 10 mg twice a day for a month or so, but he had to have the dose reduced to 5 mg twice a day. He later presented with profound anemia, a hemoglobin of 6.8 g/dL, and his platelets were 45,000 per μL. He’s still having some constitutional symptoms and splenomegaly. What would you do at this point?

Jamile Shammo, MD, FACP, FASCP: That’s so surprising to me. Obviously, you’re concerned about progression, but I also wonder what happened after you dose-reduced them. How often was he monitored? That’s what I was trying to say about when people get monitored periodically. What happened between the 10 mg and 5 mg, and how often [was he monitored]? You have to decide whether this is iatrogenic or disease progression. The pace of the cytopenia relative to dose reduction has to be assessed. Then with the stomach pain, you start to wonder whether there was initial spleen response and now resurgence of the spleen. That also has to be taken in account.

Clearly, if the practitioners determine that this is consistent with disease progression, you have to change. Obviously, you’re looking at this platelet count, and you’d have to go with an agent that would allow you to begin treatment with a platelet count below 50,000 per μL. There’s only 1 agent that you could utilize with a platelet count below 50,000 per μL: pacritinib. The critical issue in this case is to determine whether these are cytopenias induced by the agent—which would be surprising—vs disease progression.

Ruben Mesa, MD: Although determining either is important because it has implications in terms of transplant. Have they really progressed? But either way, pacritinib would still be an option. It has a couple niches. In individuals who are too sensitive to the alternative, ruxolitinib or fedratinib, and have cytopenias and thrombocytopenia, pacritinib fits in nicely. Or they were resistant or had progression so in both. But you’re right: It’s critical to determine the reason and to be sure that the reason is disease related. Thrombocytopenia less, but as a cautionary tale, I have found several secondary colon cancers, GYN [gynecological] cancers, and other reasons people have become anemic while they had myelofibrosis, due to a different cause. Always wear your hat as a hematologist and as an internist. Not all anemia is from the myelofibrosis.

Jamile Shammo, MD, FACP, FASCP: Ruben, would you do a bone marrow? We all agree probably that you’d have to evaluate the stomach pain and do an ultrasound, but what about an assessment?

Ruben Mesa, MD: The timing is very important, the dynamics. If it’s relatively soon after starting and the bone marrow has been within the last 6 months, it’s probably more the drug. But the longer time goes on, I’m mindful that time is a critical variable in the disease, and I have a relatively low threshold for repeating the bone marrow, particularly if something has changed. The diseases aren’t linear. We’ve all been surprised by the patient who seems stable but we get the call from the laboratory and they say, “Do you know that Mrs. Jones has 30% blasts in her peripheral blood?” A month ago her counts were fine, and there were no blasts.

Jamile Shammo, MD, FACP, FASCP: Indeed.

Ruben Mesa, MD: They aren’t linear. I agree; having a low threshold for repeating a bone marrow is important.

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