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Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation
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 ru...
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Published in: | Blood 2017-08, Vol.130 (9), p.1125-1131 |
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creator | Newberry, Kate J. Patel, Keyur Masarova, Lucia Luthra, Rajyalakshmi Manshouri, Taghi Jabbour, Elias Bose, Prithviraj Daver, Naval Cortes, Jorge Kantarjian, Hagop Verstovsek, Srdan |
description | 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 |
doi_str_mv | 10.1182/blood-2017-05-783225 |
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•Survival of patients with MF after ruxolitinib discontinuation is poor, with median survival of 14 months.•Low platelets at the start or end of therapy or clonal evolution while on therapy are associated with an even worse prognosis.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2017-05-783225</identifier><identifier>PMID: 28674026</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Clonal Evolution ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myeloid Neoplasia ; Primary Myelofibrosis - drug therapy ; Primary Myelofibrosis - genetics ; Primary Myelofibrosis - pathology ; Pyrazoles - therapeutic use ; Treatment Outcome ; Withholding Treatment</subject><ispartof>Blood, 2017-08, Vol.130 (9), p.1125-1131</ispartof><rights>2017 American Society of Hematology</rights><rights>2017 by The American Society of Hematology.</rights><rights>2017 by The American Society of Hematology 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-37569d74ed0a647922d9b85b2bc6f15633486c5bc74395745f5432d5603756623</citedby><cites>FETCH-LOGICAL-c529t-37569d74ed0a647922d9b85b2bc6f15633486c5bc74395745f5432d5603756623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006497120329141$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28674026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Newberry, Kate J.</creatorcontrib><creatorcontrib>Patel, Keyur</creatorcontrib><creatorcontrib>Masarova, Lucia</creatorcontrib><creatorcontrib>Luthra, Rajyalakshmi</creatorcontrib><creatorcontrib>Manshouri, Taghi</creatorcontrib><creatorcontrib>Jabbour, Elias</creatorcontrib><creatorcontrib>Bose, Prithviraj</creatorcontrib><creatorcontrib>Daver, Naval</creatorcontrib><creatorcontrib>Cortes, Jorge</creatorcontrib><creatorcontrib>Kantarjian, Hagop</creatorcontrib><creatorcontrib>Verstovsek, Srdan</creatorcontrib><title>Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation</title><title>Blood</title><addtitle>Blood</addtitle><description>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.
•Survival of patients with MF after ruxolitinib discontinuation is poor, with median survival of 14 months.•Low platelets at the start or end of therapy or clonal evolution while on therapy are associated with an even worse prognosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Clonal Evolution</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myeloid Neoplasia</subject><subject>Primary Myelofibrosis - drug therapy</subject><subject>Primary Myelofibrosis - genetics</subject><subject>Primary Myelofibrosis - pathology</subject><subject>Pyrazoles - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Withholding Treatment</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9UcFu1TAQtBCIvrb8AUI5ckm7dry2c0FCTy1UqgQHOFuO7YCRYxc7eWr_vnl9pZQLp11pd2ZnZwh5S-GMUsXOh5izaxlQ2QK2UnWM4QuyochUC8DgJdkAgGh5L-kROa71FwDlHcPX5IgpITkwsSFftzEnExu_y3GZQ06NSa7Jy2zz5GsTUjPd-ZjHMJRcQ23MOPvSlOU2xzCHFIbGhWpzWvvF7PGn5NVoYvVvHusJ-X558W37ub3-8ulq-_G6tcj6ue0kit5J7h0YwWXPmOsHhQMbrBgpiq7jSlgcrORdj5LjiKt2hwL2SMG6E_LhwHuzDJN31qe5mKhvSphMudPZBP3vJIWf-kfeaUQFTOJK8P6RoOTfi6-zntZPfIwm-bxUTXuKSlFQ_brKD6t2NaEWPz6doaD3YeiHMPQ-DA2oD2GssHfPJT6B_rj_9we_GrULvuhqg0_Wu1C8nbXL4f8X7gH0g5zZ</recordid><startdate>20170831</startdate><enddate>20170831</enddate><creator>Newberry, Kate J.</creator><creator>Patel, Keyur</creator><creator>Masarova, Lucia</creator><creator>Luthra, Rajyalakshmi</creator><creator>Manshouri, Taghi</creator><creator>Jabbour, Elias</creator><creator>Bose, Prithviraj</creator><creator>Daver, Naval</creator><creator>Cortes, Jorge</creator><creator>Kantarjian, Hagop</creator><creator>Verstovsek, Srdan</creator><general>Elsevier Inc</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170831</creationdate><title>Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation</title><author>Newberry, Kate J. ; Patel, Keyur ; Masarova, Lucia ; Luthra, Rajyalakshmi ; Manshouri, Taghi ; Jabbour, Elias ; Bose, Prithviraj ; Daver, Naval ; Cortes, Jorge ; Kantarjian, Hagop ; Verstovsek, Srdan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-37569d74ed0a647922d9b85b2bc6f15633486c5bc74395745f5432d5603756623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Clonal Evolution</topic><topic>Female</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myeloid Neoplasia</topic><topic>Primary Myelofibrosis - drug therapy</topic><topic>Primary Myelofibrosis - genetics</topic><topic>Primary Myelofibrosis - pathology</topic><topic>Pyrazoles - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Withholding Treatment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Newberry, Kate J.</creatorcontrib><creatorcontrib>Patel, Keyur</creatorcontrib><creatorcontrib>Masarova, Lucia</creatorcontrib><creatorcontrib>Luthra, Rajyalakshmi</creatorcontrib><creatorcontrib>Manshouri, Taghi</creatorcontrib><creatorcontrib>Jabbour, Elias</creatorcontrib><creatorcontrib>Bose, Prithviraj</creatorcontrib><creatorcontrib>Daver, Naval</creatorcontrib><creatorcontrib>Cortes, Jorge</creatorcontrib><creatorcontrib>Kantarjian, Hagop</creatorcontrib><creatorcontrib>Verstovsek, Srdan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Newberry, Kate J.</au><au>Patel, Keyur</au><au>Masarova, Lucia</au><au>Luthra, Rajyalakshmi</au><au>Manshouri, Taghi</au><au>Jabbour, Elias</au><au>Bose, Prithviraj</au><au>Daver, Naval</au><au>Cortes, Jorge</au><au>Kantarjian, Hagop</au><au>Verstovsek, Srdan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2017-08-31</date><risdate>2017</risdate><volume>130</volume><issue>9</issue><spage>1125</spage><epage>1131</epage><pages>1125-1131</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><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.
•Survival of patients with MF after ruxolitinib discontinuation is poor, with median survival of 14 months.•Low platelets at the start or end of therapy or clonal evolution while on therapy are associated with an even worse prognosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28674026</pmid><doi>10.1182/blood-2017-05-783225</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Aged, 80 and over Clonal Evolution Female Humans Kaplan-Meier Estimate Male Middle Aged Myeloid Neoplasia Primary Myelofibrosis - drug therapy Primary Myelofibrosis - genetics Primary Myelofibrosis - pathology Pyrazoles - therapeutic use Treatment Outcome Withholding Treatment |
title | Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation |
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