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EHA 2024

Management of cytopenic myelofibrosis

August 22, 2024

Presented by Dr Adriano Salaroli (Institut Jules Bordet, Brussels, Belgium)

Dr Adriano Salaroli, a haematologist at the Institut Jules Bordet in Brussels, provides an update on cytopenic myelofibrosis, emphasising the need for increased awareness regarding this specific subtype of myelofibrosis.

Cytopenic myelofibrosis is primarily characterised by significant cytopenias, particularly anaemia and thrombocytopenia. The issue of cytopenia is not limited to the initial diagnosis; patients with the myeloproliferative phenotype of myelofibrosis frequently develop anaemia, and a significant majority will experience thrombocytopenia, either due to disease progression or as a consequence of therapeutic interventions.

From a clinical perspective, these patients are distinguished by an elevated risk of infection and bleeding, making their management more challenging compared to those with the classical myeloproliferative form of the disease. Both anaemia and thrombocytopenia are prevalent in these patient populations, complicating the use of standard therapies such as JAK inhibitors. The need arises for a therapeutic approach that can effectively control constitutional symptoms and manage splenomegaly while minimising toxicity to haemoglobin and platelet levels. This consideration is critical because dose reductions of JAK inhibitors, often necessary to mitigate haematologic toxicity, can negatively impact symptom control and spleen volume reduction. While ancillary treatments, such as erythropoietin or thrombopoietin, may offer some benefit, their efficacy is often limited by a lack of durable responses. 

Recently, new JAK inhibitors have emerged with a reduced toxicity profile, allowing for administration at optimal therapeutic doses. Momelotinib, a JAK1/JAK2/ACVR1 inhibitor, has been specifically indicated for the management of myelofibrosis patients with anaemia. This drug has demonstrated promising results in cytopenic myelofibrosis patients. Another notable drug is pacritinib, a JAK2 inhibitor that also targets several other tyrosine kinases. It is indicated for the treatment of symptomatic myelofibrosis in patients with a platelet count below 50,000/µL, making it particularly relevant for patients presenting with low platelet counts at the onset of the disease. 

Future research is expected to focus on exploring combination therapies that involve multiple JAK inhibitors. Such strategies hold the potential to enhance treatment efficacy by targeting different pathways within the disease process while also mitigating the toxicities associated with single-agent therapies.

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