Journal Article

A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis

Vaddi, Kris, Gotlib, Jason, Verstovsek, Srdan, Raza, Azra, Paquette, Ronald, Sun, William, Levy, Richard S, Deininger, Michael, Harvey, Jimmie H, Catalano, John V, Winton, Elliott F, Arcasoy, Murat O, Lyons, Roger M, DiPersio, John F, Talpaz, Moshe, Koumenis, Iphigenia L, Silver, Richard T, Hexner, Elizabeth, Mesa, Ruben A, Gupta, Vikas, Erickson-Viitanen, Susan, Miller, Carole, Sandor, Victor, Kantarjian, Hagop M

2012

Overview

This trial showed clinically significant responses in spleen size and quality of life among patients with myelofibrosis receiving ruxolitinib, a JAK1 and JAK2 inhibitor. The agent has some myelotoxicity, but this study showed a survival advantage with ruxolitinib. Myelofibrosis, a myeloproliferative neoplasm, is manifested by abnormal blood counts (anemia, thrombocytosis or thrombocytopenia, and leukocytosis or leukopenia), splenomegaly, and debilitating symptoms (e.g., fatigue, weakness, abdominal pain, cachexia, weight loss, pruritus, night sweats, and bone pain), which are thought to be caused by the combined effects of massive splenomegaly and elevated levels of proinflammatory cytokines. 1 Survival ranges from approximately 2 to 11 years, depending on defined prognostic factors. 2 Traditional therapeutic options, including splenectomy, have limited benefit. 3 Although allogeneic stem-cell transplantation may cure myelofibrosis, few patients are eligible for this treatment. Although the gain-of-function mutation in the gene encoding Janus kinase . . .

• Publisher: Massachusetts Medical Society
• Subject: Acute myeloid leukemia / Adult / Aged / Aged, 80 and over / Anemia / Biological and medical sciences / Blood platelets / Cell Transformation, Neoplastic / Clinical significance / Clinical trials / Cytokines / Double-Blind Method / Double-blind studies / Enzyme inhibitors / Female / Follow-Up Studies / General aspects / Hematologic and hematopoietic diseases / Humans / Inhibitor drugs / Intention to Treat Analysis / Janus kinase / Janus Kinase 1 - antagonists & inhibitors / Janus Kinase 2 - antagonists & inhibitors / Kaplan-Meier Estimate / Kinases / Leukemia, Myeloid, Acute - mortality / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Magnetic resonance imaging / Male / Medical research / Medical sciences / Medical treatment / Middle Aged / Myelofibrosis / Myeloid leukemia / Nitriles / Organ Size / Patients / Primary Myelofibrosis - drug therapy / Primary Myelofibrosis - mortality / Primary Myelofibrosis - pathology / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - therapeutic use / Pyrazoles - adverse effects / Pyrazoles - therapeutic use / Pyrimidines / Quality of Life / Spleen / Spleen - drug effects / Spleen - pathology / Splenomegaly - drug therapy / Survival / Targeted cancer therapy / Thrombocytopenia