Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation
Kate J Newberry, Keyur Patel, Lucia Masarova, Rajyalakshmi Luthra, Taghi Manshouri, Elias Jabbour, Prithviraj Bose, Naval Daver, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek, Kate J Newberry, Keyur Patel, Lucia Masarova, Rajyalakshmi Luthra, Taghi Manshouri, Elias Jabbour, Prithviraj Bose, Naval Daver, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek
Abstract
Despite significant improvements in the signs and symptoms of myelofibrosis (MF), and possible prolongation of patients' survival, some have disease that is refractory to ruxolitinib and many lose their response over time. Furthermore, patients with ≥3 mutations are less likely to respond to ruxolitinib. Here we describe outcomes after ruxolitinib discontinuation in MF patients enrolled in a phase 1/2 study at our center. After a median follow-up of 79 months, 86 patients had discontinued ruxolitinib (30 of whom died while on therapy). The median follow-up after ruxolitinib discontinuation for the remaining 56 patients was 32 months, with median survival after discontinuation of 14 months. Platelets <260 × 109/L at the start of therapy or <100 × 109/L at the time of discontinuation were associated with shorter survival after discontinuation. Of 62 patients with molecular data at baseline and follow-up, 22 (35%) acquired a new mutation while receiving ruxolitinib (14 [61%] in ASXL1). Patients showing clonal evolution had significantly shorter survival after discontinuation (6 vs 16 months). Transfusion dependency was the only clinical variable associated with clonal evolution. These findings underscore the need for novel therapies and suggest that clonal evolution or decreasing platelet counts while on ruxolitinib therapy may be markers of poor prognosis.
Conflict of interest statement
Conflict-of-interest disclosure: S.V. receives research funding from Incyte Corporation. The remaining authors declare no competing financial interests.
© 2017 by The American Society of Hematology.
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Source: PubMed