Considering Cytopenias in the Management of Myelofibrosis

patient care perspectives by Raajit K. Rampal, MD, PhD

Anemia and thrombocytopenia are common complications in patients with myelofibrosis, and they have clear prognostic implications. Appropriate management is essential to optimize clinical outcomes. When choosing therapy, it is important to understand the differing effects of the available agents on red blood cell and platelet levels.

Expert Commentary
“I think that the early identification and management of cytopenias such as anemia are important because, in my opinion, you should not wait for anemia-related consequences to manifest before treating the patient.”
— Raajit K. Rampal, MD, PhD

The development of cytopenias in a patient with myelofibrosis has both management and prognostic implications. It could necessitate a change in treatment, such as switching a patient to a new JAK inhibitor, and it may also lead a clinician to consider an earlier referral for stem cell transplantation. In patients who have anemia or are likely to develop anemia, there is certainly a prognostic element because someone who becomes red blood cell transfusion dependent is likely to have a worse prognosis. If that occurs, and if we can determine that it is not entirely due to their JAK inhibitor therapy, that is a patient I would prioritize for getting a stem cell transplant. The same is true of thrombocytopenia. For a patient with preserved platelets and who is feeling fine, we may keep them on their current therapy; however, for a patient with worsening thrombocytopenia, there is a risk of disease progression. That is somebody I would prioritize for a stem cell transplant.


I think that the early identification and management of cytopenias such as anemia are important because, in my opinion, you should not wait for anemia-related consequences to manifest before treating the patient. There are consequences when patients progress to becoming red blood cell transfusion dependent, as these individuals may then develop iron overload over time, leading to problems with the liver and, sometimes, the heart. Thus, if you head off the cytopenia early or if you limit its duration, the patient is likely to benefit over the long-term. I have no doubt about that.


There are some potential differences between JAK inhibitors with respect to their effects on red blood cells and platelets. Momelotinib is currently indicated for the treatment of patients with myelofibrosis and anemia. I think that we may move more toward using this agent in these patients with anemia, but the clinical implications of anemia are relative; some patients are anemic but do not need transfusions, whereas others do. Will we move toward using momelotinib as the standard of care for all patients with myelofibrosis who have a hemoglobin level of less than 10 g/dL? Or will we reserve it for use in those who do not do well with ruxolitinib? We do not know the answer to these questions yet.


For patients with thrombocytopenia, the answer is more clear-cut. If the patient is on ruxolitinib and has a platelet level of less than 50,000/µL, switching to pacritinib is a clear choice. Momelotinib can be used in patients with a platelet count of 25,000/µL as well. Pacritinib more recently has demonstrated a potential anemia benefit, but it is not yet indicated for this. Although we do not yet have any data comparing the potential anemia benefits of pacritinib vs momelotinib, additional clinical studies will hopefully help us to better define the role of each therapy in patients who develop these cytopenias.


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Gerds AT, Verstovsek S, Vannucchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study. Lancet Haematol. 2023;10(9):e735-e746. doi:10.1016/S2352-3026(23)00174-6


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Oh ST, Mesa RA, Harrison CN, et al. Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood Adv. 2023;7(19):5835-5842. doi:10.1182/bloodadvances.2023010151


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Verstovsek S. How I manage anemia related to myelofibrosis and its treatment regimens. Ann Hematol. 2023;102(4):689-698. doi:10.1007/s00277-023-05126-4

Raajit K. Rampal, MD, PhD

Associate Member
Clinical Director, Leukemia Service
Director, Myeloproliferative Neoplasms Program
Memorial Sloan Kettering Cancer Center
New York, NY