Treatment advancements in myelofibrosis are translating into more options for patients with anemia and cytokine-driven symptoms or splenomegaly. Such advancements may allow for a greater individualization of treatment in the coming years, with the ultimate goal of impacting survival and improving quality of life.

The treatment of myelofibrosis has advanced light years from where it was when I began to practice in 2013. At that time, all that we had available were ruxolitinib and hydroxyurea. Now we have multiple JAK inhibitors and non-JAK agents, and our JAK inhibitors have mechanistic differences that may be relevant in patients with different cytopenic profiles. Other drugs such as luspatercept, which is US Food and Drug Administration (FDA) approved now in myelodysplastic syndrome, are beginning to be studied for anemia in myelofibrosis. The clinical benefits that are associated with these agents vary, and this is an area that is just now emerging and continues to be studied.

We do not yet know whether a paradigm will develop in which a patient with low platelets might receive pacritinib and a patient with anemia might receive momelotinib. If you have a patient on ruxolitinib and they develop or have anemia, are you going to put them on pacritinib or are you going to put them on momelotinib? It is an important question, and we do not yet have an answer. We are guided, to a certain extent, by the clinical trial data and the product labels.

This is the most clear-cut in patients with significant thrombocytopenia. Data from the phase 3 PERSIST-1 and -2 trials demonstrated that pacritinib is an effective treatment for patients with myelofibrosis and severe thrombocytopenia. The FDA gave pacritinib an approval based on spleen volume reduction in patients with platelet counts of less than 50×10³/µL. So, if you have a patient with significant thrombocytopenia, the decision becomes a little easier.

In the phase 3 MOMENTUM trial, approximately 30% of patients with myelofibrosis and anemia achieved transfusion independence with momelotinib. The FDA-approved indication for momelotinib is for the treatment of myelofibrosis in adults with anemia. This gives us another treatment option, particularly for those with anemia, and I am very happy about that. However, with regard to anemia in myelofibrosis, we still need to tease out what we mean by anemia. For example, are we talking about the patient with a hemoglobin of 9 g/dL or the patient with a hemoglobin of 7 g/dL?

Regarding safety, we have the longest experience with ruxolitinib, which most people will use in the front line. There are some differences between JAK inhibitors with regard to the risk of developing cytopenias such as anemia and thrombocytopenia. However, it is important to note that this is one of many possible treatment considerations; it really comes down to what you are trying to treat, how you are trying to treat it, and what drug might interact best with the patient. For individuals with more preserved blood counts, fedratinib and ruxolitinib have both shown good efficacy in the first line in phase 3 trials; with fedratinib, there can be a fair amount of gastrointestinal toxicity, which can be mitigated, but you have to think about that in the context of the patient’s other ongoing medical issues and whether or not they can tolerate that.

To summarize, we now have JAK inhibitor therapies that work differently mechanistically, and this is tremendously exciting. We need to see the long-term data with these therapies to understand their impact more fully, and, ultimately, we need to know whether patients are living better and longer. The potential is absolutely there, but we do not know the answer to these questions yet.