المؤلفون: Stein, Brady L, Gotlib, Jason, Arcasoy, Murat, Nguyen, Marie Huong, Shah, Neil, Moliterno, Alison, Jamieson, Catriona, Pollyea, Daniel A, Scott, Bart, Wadleigh, Martha, Levine, Ross, Komrokji, Rami, Klisovic, Rebecca, Gundabolu, Krishna, Kropf, Patricia, Wetzler, Meir, Oh, Stephen T, Ribeiro, Raul, Paschal, Rita, Mohan, Sanjay, Podoltsev, Nikolai, Prchal, Josef, Talpaz, Moshe, Snyder, David, Verstovsek, Srdan, Mesa, Ruben A

المصدر: Journal of the National Comprehensive Cancer Network. 13(4)

مصطلحات موضوعية: Rare Diseases, Hematology, Antineoplastic Agents, Calreticulin, Hematopoietic Stem Cell Transplantation, Humans, Hydroxyurea, Janus Kinase 2, Janus Kinases, Polycythemia Vera, Primary Myelofibrosis, Protein Kinase Inhibitors, Receptors, Thrombopoietin, Splenomegaly, Thrombocythemia, Essential, Thrombosis, Oncology & Carcinogenesis

الوصف: The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for hematologists/oncologists, and are discussed in this article.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/29k8f86rTest

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

المصدر: New England Journal of Medicine. 3/1/2012, Vol. 366 Issue 9, p799-807. 9p. 3 Diagrams.

مصطلحات موضوعية: *PROTEIN kinase inhibitors, *MYELOFIBROSIS, *PLACEBOS, *SPLEEN, *ANEMIA, *THROMBOCYTOPENIA, *THERAPEUTICS

مستخلص: Background: Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis. Methods: In this double-blind trial, we randomly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients). The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic resonance imaging. Secondary end points included the durability of response, changes in symptom burden (assessed by the total symptom score), and overall survival. Results: The primary end point was reached in 41.9% of patients in the ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A reduction in spleen volume was maintained in patients who received ruxolitinib; 67.0% of the patients with a response had the response for 48 weeks or more. There was an improvement of 50% or more in the total symptom score at 24 weeks in 45.9% of patients who received ruxolitinib as compared with 5.3% of patients who received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence interval, 0.25 to 0.98; P=0.04). The rate of discontinuation of the study drug because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the placebo group. Among patients who received ruxolitinib, anemia and thrombocytopenia were the most common adverse events, but they rarely led to discontinuation of the drug (in one patient for each event). Two patients had transformation to acute myeloid leukemia; both were in the ruxolitinib group. Conclusions: Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.) [ABSTRACT FROM PUBLISHER]