Myelofibrosis (MF), including primary MF and MF secondary to polycythemia vera or essential thrombocythemia, is a chronic, clinically heterogeneous hematologic malignancy characterized by inefficient hematopoiesis, bone marrow fibrosis, and shortened survival. Typical clinical manifestations include progressive splenomegaly, debilitating symptoms, and anemia. MF is associated with dysregulation of Janus kinase (JAK)-signal transducer and activator of transcription (JAK/STAT) pathway affecting hematopoiesis and inflammation. Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved for the treatment of patients with intermediate or high-risk MF based on the results of 2 phase 3 studies (Controlled MyeloFibrosis Study with Oral JAK Inhibitor Treatment [COMFORT]-I and COMFORT-II). In these trials, ruxolitinib treatment was associated with reductions in spleen size and symptom burden, and improvements in quality of life. The most common adverse events were dose-dependent cytopenias, which were managed by dose modifications, treatment interruptions, and red blood cell transfusions (for anemia). Ruxolitinib was effective regardless of MF type, risk status, or JAK2V617F mutation status, and across various other MF subpopulations. Two-year follow-up data from the COMFORT trials also demonstrate that ruxolitinib has durable efficacy and may be associated with a survival advantage relative to placebo and best available therapy. Preliminary data from ongoing studies support possible dosing strategies for patients with low platelet counts.
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