Fedratinib in the treatment of myelofibrosis and challenges of treating anemia with JAK2 inhibitors

Abstract: Anemia is common in patients with myelofibrosis. It is one of the manifestations of the disease due to ineffective hematopoiesis (the production of blood cells) and sequestration of blood cells in the spleen. The current main drug choices for myelofibrosis (ruxolitinib, fedratinib) aim to alleviate symptoms by inhibiting the Janus kinase pathway, which is uniformly upregulated in MF patients. Clinical trials involving fedratinib showed that fedratinib significantly reduced spleen volume and improved symptom burden compared to the placebo, however the effect on anemia remains unclear. The FREEDOM 2 clinical study showed a beneficial effect on the number of platelets and thrombopoiesis, and the possibility of using fedratinib in patients with mild to moderate thrombocytopenia. These patients would necessarily require a dose reduction of ruxolitinib if this drug were selected, but could receive full-dose fedratinib that allows for more potent suppression of abnormal JAK pathway activation. For those patients with MF who develop anemia, careful patient management, including red blood cell transfusions, secondary anemia treatments, JAK inhibitor dose modifications, and monitoring, can improve the anemia to prevent further disease complications and improve clinical outcomes. Different JAK inhibitors can now be tailored to the individual patients based on their associated comorbidities and cytopenias

Key words:
anemia; JAK2 inhibitors; fedratinib; myelofibrosis