<p>We have drugs to address myelofibrosis symptoms and spleen size, but we have not been as successful with drugs to improve anemia and thrombocytopenia in patients with myelofibrosis. Severe cytopenias can impact a patient’s quality of life (QOL) and are associated with a worsened prognosis and survival, so providing appropriate and early intervention to prevent transfusion dependence is important.</p>

Once people develop transfusion dependence, it is usually very hard for them to ever achieve and maintain transfusion independence. Therefore, it is best to act proactively and decrease the transfusion frequency as soon as possible before transfusion dependence develops. We have 2 JAK inhibitors with US Food and Drug Administration (FDA) approval for patients with myelosuppression: pacritinib and momelotinib. Pacritinib is indicated for patients with platelet counts of less than 50,000/μL. Momelotinib does not have an indication based on platelet count but has one for anemia, and it has been studied in patients with lower platelet counts (as low as 25,000/μL).

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For patients with very severe thrombocytopenia characterized by fewer than 25,000/μL platelets, pacritinib is the only FDA-approved agent for use in clinical practice. For patients with platelet counts of 25,000/μL to 50,000/μL, we can also choose momelotinib, but the monitoring of platelets at the start of therapy is needed. If somebody has a platelet count of approximately 50,000/μL and severe anemia or severe transfusion dependence, momelotinib is preferred because of the treatment effect on the anemia that occurs much faster with the use of this agent. For patients with less transfusion dependence and lower platelet counts, pacritinib may be the best agent.

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I would caution that, while we treat the disease and help patients with myelofibrosis to be less symptomatic, we often will not improve their platelet counts to what we would expect as a hematologic response. For patients with anemia, momelotinib leads to transfusion independence more frequently and improves hemoglobin levels faster than pacritinib, but it is important to recognize that pacritinib is typically used in patients who are also very thrombocytopenic, so the mechanisms behind their pathologies are likely more complex.

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When a therapy is chosen, it has to be given time to work. Therefore, after choosing a therapy, I would advise trying it for at least 3 to 4 months to see what can be achieved. I would caution against choosing 1 drug and then switching to the other if the patient’s platelet count declines or if you do not see a response within 1 month (in the absence of concerning toxicity/tolerance issues).

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Anemia has historically been connected with worse outcomes in myelofibrosis. The degree of anemia and the need for transfusions matter, as do the individual patient’s symptom tolerance and the association with other factors that can also drive the outcome. Importantly, although ruxolitinib and fedratinib frequently lead to treatment-emergent anemia, this does not seem to negatively impact patient responses or outcomes, apart from this very frequently resulting in a dosage decrease, which may shorten the treatment duration and lead to treatment discontinuation.

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I think that QOL is a very important measure in myelofibrosis, and the impact of anemia can be quite significant for patient well-being because of its impact on a person’s ability to do everyday activities. There have been well-established improvements in patient-reported outcomes demonstrated with the use of JAK inhibitors in myelofibrosis. JAK inhibitors were FDA approved essentially based on their QOL benefits, such as symptom relief and spleen improvements, as we did not have any idea about whether they could extend survival. None of the trials were powered enough or were initially set up for showing a survival extension, but the data suggest that treated patients live longer, likely due to the suppression of disease burden and inflammation.