TY - JOUR
T1 - Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation
AU - Newberry, Kate J.
AU - Patel, Keyur
AU - Masarova, Lucia
AU - Luthra, Rajyalakshmi
AU - Manshouri, Taghi
AU - Jabbour, Elias
AU - Bose, Prithviraj
AU - Daver, Naval
AU - Cortes, Jorge
AU - Kantarjian, Hagop
AU - Verstovsek, Srdan
N1 - Funding Information:
Conflict-of-interest disclosure: S.V. receives research funding from Incyte Corporation. The remaining authors declare no competing financial interests.
Funding Information:
This research was supported in part by a Cancer Center Support grant to MD Anderson Cancer Center from the National Cancer Institute, National Institutes of Health (P30 CA016672).
Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/8/31
Y1 - 2017/8/31
N2 - 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 x 109/L at the start of therapy or <100 x 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.
AB - 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 x 109/L at the start of therapy or <100 x 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.
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U2 - 10.1182/blood-2017-05-783225
DO - 10.1182/blood-2017-05-783225
M3 - Article
C2 - 28674026
AN - SCOPUS:85028864163
SN - 0006-4971
VL - 130
SP - 1125
EP - 1131
JO - Blood
JF - Blood
IS - 9
ER -