A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis

Abstract

Myelofibrosis is a hematological malignancy with a median survival of approximately 5 to 7 years. Allogeneic stem cell transplantation is the only therapeutic modality that provides a cure for myelofibrosis patients. Recently, ruxolitinib has been shown in 2 phase 3 studies to be effective in reducing splenomegaly and improving symptoms in myelofibrosis patients. Although conventional markers of disease burden (marrow histopathological features, cytogenetic and molecular markers, and reversal of cytopenias) were not uniformly improved, a survival advantage in favor of ruxolitinib therapy was demonstrated. The use of historical control cohorts to compare survival was implemented in 2 different analyses of patients enrolled in the phase 1/2 studies and has further added fuel to the controversy surrounding the significance of this survival advantage. Ruxolitinib therapy results in a dramatic reduction in circulating proinflammatory cytokine levels, which has been associated with improvement in symptoms and performance status and may provide a link to improved survival. We analyze the various data published and place in perspective the significance of the prolongation of survival associated with ruxolitinib therapy. This critical review of these data may allow physicians to more rationally assess the benefits that can be anticipated with the appropriate use of this therapy. © 2013 by The American Society of Hematology.