Advances in Myelofibrosis Management: New Janus Kinase Inhibitors Beyond Ruxolitinib

Myelofibrosis is a myeloproliferative neoplasm characterized by the buildup of fibrous scar tissue in the bone marrow occurring secondary to the secretion of inflammatory cytokines, leading to cytopenias, dysfunctional hematopoiesis, and constitutional symptoms. One of the pathologic mechanisms that underlies myelofibrosis is aberrant activation of the Janus kinase (JAK)-STAT pathway. Targeting the JAK-STAT pathway via JAK inhibition can lead to significant improvements in spleen volume reduction and symptom improvement in intermediate- and high-risk myelofibrosis. The first JAK inhibitor approved by the US Food & Drug Administration was ruxolitinib in 2011. Recently, there have been additional JAK inhibitors approved for myelofibrosis, including fedratinib, pacritinib, and momelotinib. The emergence of these new therapies offers additional treatment options for patients with myelofibrosis. This article reviews the pharmacology, efficacy, safety, dosing, administration, and implications for advanced practitioners of newer JAK inhibitors (fedratinib, pacritinib, and momelotinib) in the treatment of myelofibrosis.