期刊
EXPERT OPINION ON PHARMACOTHERAPY
卷 12, 期 10, 页码 1597-1611出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/14656566.2011.568939
关键词
demethylating agents; histone deacetylase inhibitors; JAK2 inhibitors; JAK2 V617F mutation; mTOR inhibitors; myelofibrosis; myeloproliferative neoplasm; response criteria
Introduction: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies. Areas covered: This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2-inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010. Expert opinion: Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
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