Treatment approaches for myelofibrosis after disease progression

Rami Komrokji, MD: This patient received ruxolitinib 10 mg twice daily for about a month, but had to reduce the dose to 5 mg twice daily. He then presented with profound anemia, a hemoglobin of 6.8 g/dL and his platelets were 45,000 per μL. He still has constitutional symptoms and splenomegaly. What would you do at this point?

Jamile Shammo, MD, FACP, FACP: It’s so surprising to me. Obviously you’re concerned about the progression, but I’m also wondering what happened after you reduced them in dose. How often was it monitored? That’s what I was trying to say about when people are monitored periodically. What happened between 10mg and 5mg, and how often [was he monitored]? You have to decide if this is iatrogenic or disease progression. The rate of cytopenia relative to dose reduction should be assessed. Then with the stomach pain you begin to wonder if there was an initial spleen response and now a resurgence of the spleen. This too must be taken into account.

Obviously, if practitioners determine this is consistent with disease progression, you need to switch. Obviously, you are looking at that platelet count and you should opt for an agent that would allow you to start treatment with a platelet count below 50,000 per μL. There is only one agent you can use with a platelet count below 50,000 per μL: pacritinib. The crucial question in this case is whether it is agent-induced cytopenias – which would be surprising – vs disease progression.

Ruben Mesa, MD: Although determining one or the other is important as it has implications in terms of transplantation. Have they really progressed? But either way, pacritinib would still be an option. It has a few niches. In people who are too sensitive to the alternative, ruxolitinib or fedratinib, and who have cytopenias and thrombocytopenias, pacritinib is ideal. Or they were resistant or had progression in both cases. But you are right: it is essential to determine the reason and to ensure that the reason is related to the disease. Thrombocytopenia less, but as a caveat I found several secondary colon cancers, GYN [gynecological] cancers and other reasons why people became anemic when they had myelofibrosis, due to a different cause. Always wear your hematologist and internist hat. Not all anemias result from myelofibrosis.

Jamile Shammo, MD, FACP, FACP: Ruben, would you make a marrowbone? We’re probably all in agreement that you should assess 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 onset and the bone marrow has been within the last 6 months, it’s probably more the drug. But the more time passes, the more I am aware that time is a critical variable in disease, and I have a relatively low threshold to repeat bone marrow, particularly if something has changed. Diseases are not linear. We were all surprised by the patient who seems stable but we get the call from the lab and they say, “Do you know Mrs. Jones has 30% blasts in her peripheral blood?” A month ago, his accounts were good and there were no outbursts.

Jamile Shammo, MD, FACP, FACP: In effect.

Ruben Mesa, MD: They are not linear. I agree; having a low threshold to repeat a bone marrow is important.

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