A look at sequencing strategies for myelofibrosis treatments.
John Mascarenhas, MD: Srdan, broadly speaking, we have 3 drugs, so one can envision sequencing these JAK inhibitors. If you were to break the patients down, either by cytopenic or proliferative phenotype myelofibrosis, or even by risk status, how are you lining up the drugs? Is there a thought process as to which drug you might choose first and where you might go second or even third?
Srdan Verstovsek, MD, PhD: Let’s base our discussion on the NCCN [National Comprehensive Cancer Network] guidelines, because they’re excellent in providing clues on what to do first. I’d start by dividing patients into lower- and higher-risk categories, because lower-risk patients usually aren’t anemic. That would be exceptional. They may be older and have some blasts or symptoms, but in general, they aren’t that bad in terms of clinical problems.
High-risk patients are the ones we have talked about so far through discussion today, and they’re in the need of very good therapy. One can observe lower-risk patients if they have no problems. Or if they’re proliferative in nature by having high platelets or a high white blood cell count, one can even choose hydroxyurea or interferon. This will be prefibrotic myelofibrosis or those who come from ET [essential thrombocythemia] and PV [polycythemia vera] into the myelofibrosis field but still have high counts.
An occasional patient with symptomatic splenomegaly can exist in the lower-risk category. Because they have a good count, I’d usually use ruxolitinib. In high-risk groups, patients may have low platelets, be more anemic, or have a very big spleen or bad quality of life. The blood count has a major role in what we decide to do for them. We’ll choose a different dose of ruxolitinib based on platelet count. If the platelets are very low, we’ll use pacritinib. In the frontline setting, it’s basically pacritinib for low platelets, very low platelets, and otherwise ruxolitinib if the platelets are relatively preserved.
Anemia has some influence on my practice as well. Anemia many times appears with low platelet counts. If the patients are at risk of a worsening blood cell count through the use of ruxolitinib, I’d start at a lower dose, 10 mg twice a day. I learned from John. Then I’d go from 10 to 15 mg and maybe to 20 mg if I can, and optimize the care by providing the highest safe dose of ruxolitinib. In other words, if you want to make it simpler, for low platelet numbers, I use pacritinib. Otherwise, I use ruxolitinib, perhaps in different ways, using different doses. It depends on degree of anemia and degree of thrombocytopenia. In general, I’m starting lower and building it up.
In the second-line setting, if the patients are failing because of uncontrolled spleen and symptoms but still have a good bone marrow reserve, fedratinib comes to mind. If the platelets are low and patients are anemic, then pacritinib would be the choice. Clearly, the distinction between the 2 groups of patients in the second line is based on blood cell count. As far as the nonmyelosuppressive vs myelosuppressive drug, you’ll choose one over the other based on patient characteristics.
Transcript edited for clarity.