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• W1981888767 abstract "Summary Myelofibrosis ( MF ) is a P hiladelphia chromosome–negative stem cell myeloproliferative neoplasm ( MPN ) associated with cytopenias, splenomegaly, constitutional symptoms, and poor prognosis. MF patients commonly express JAK 2 V 617 F mutation and activation of J anus kinase ( JAK )/signal transducer and activator of transcription ( STAT ) signalling. Agents targeting the JAK / STAT pathway have demonstrated efficacy in patients with MF . This study evaluated panobinostat, a pan‐deacetylase inhibitor that depletes JAK 2 V 617 F levels and JAK / STAT signalling in MPN cells, in patients with primary MF , post–essential thrombocythaemia MF , and post–polycythaemia vera MF . Patients received panobinostat 40 mg administered three times per week. Dose reductions were permitted for toxicities. The primary endpoint was response rate at 6 months using I nternational W orking G roup for M yelofibrosis R esearch and T reatment ( IWG ‐ MRT ) consensus criteria. Analyses of peripheral blood cells from treated patients revealed that panobinostat inhibited JAK / STAT signalling, decreased inflammatory cytokine levels, and decreased JAK 2 V 617 F allelic burden. However, panobinostat was poorly tolerated at the dose and schedule evaluated, and only 16 of 35 patients completed ≥2 cycles of treatment. One patient (3%) achieved an IWG ‐ MRT response. Common adverse events were thrombocytopenia (71·4%) and diarrhoea (80·0%). Although molecular correlative analyses suggested that panobinostat inhibits key intracellular targets, limited clinical activity was observed because of poor tolerance." @default.
• W1981888767 created "2016-06-24" @default.
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• W1981888767 date "2013-05-23" @default.
• W1981888767 modified "2023-10-04" @default.
• W1981888767 title "Phase II trial of panobinostat, an oral pan-deacetylase inhibitor in patients with primary myelofibrosis, post-essential thrombocythaemia, and post-polycythaemia vera myelofibrosis" @default.
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• W1981888767 doi "https://doi.org/10.1111/bjh.12384" @default.
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