JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis

Patients with myelofibrosis who were treated with ruxolitinib, a JAK1 and JAK2 inhibitor, showed significant responses with respect to spleen size and quality of life. No effect on overall survival was seen, but one third of the patients assigned to the best available therapy could not be evaluated. Myelofibrosis, which can present as a primary disease or can evolve from polycythemia vera or essential thrombocythemia, 1 is characterized by marrow fibrosis, progressive anemia, and extramedullary hematopoiesis, manifested primarily as splenomegaly. Severe constitutional symptoms (e.g., night sweats and weight loss), pruritus, fatigue, and sequelae of splenomegaly are common. 2 The median survival from the time of diagnosis is 4 years for patients with intermediate-2–risk disease and 2 years for patients with high-risk disease. 3 Apart from allogeneic stem-cell transplantation, treatment is palliative and does not address the characteristic abnormality identified in myelofibrosis, a dysregulation of Janus kinase (JAK)–mediated cytokine and growth-factor signal . . .