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Novel treatment strategies for myeloproliferative neoplasms.

Bose, Prithviraj; Masarova, Lucia; Verstovsek, Srdan.
Rinsho Ketsueki; 60(9): 1176-1185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597841
Although the Janus kinase (JAK) inhibitor ruxolitinib has long been the only drug licensed for treatment of the classic Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms, years of drug development efforts have begun to bear fruit with the recent approval of a novel monopegylated interferon alfa-2b, ropeginterferon alfa, for patients with polycythemia vera without symptomatic splenomegaly in Europe. Several newer JAK inhibitors (fedratinib, pacritinib, momelotinib) have shown activity in phase 3 trials in patients with myelofibrosis but have, for various reasons, not yet received regulatory approval; all these agents, however, remain in active clinical development. Many other agents with diverse mechanisms of action are being explored in clinical trials in patients with myelofibrosis, both as single agents and in combination with ruxolitinib. Besides splenomegaly and symptoms, improvement of anemia has become a new focus of drug development in myelofibrosis. Ruxolitinib appears promising also in chronic neutrophilic leukemia, where mutations in CSF3R are common. Pemigatinib, a potent and selective inhibitor of fibroblast growth factor receptor (FGFR), has shown impressive efficacy in a small registration-directed trial in patients with FGFR1-rearranged myeloid/lymphoid neoplasms. Finally, avapritinib, a highly potent and selective inhibitor of KITD816V, has demonstrated unprecedented response rates in patients with advanced systemic mastocytosis.
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