{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:51:28Z","timestamp":1790754688883,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011726","name":"Wessex Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011726","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Ibrutinib is associated with response rate of 90% and median progression\u2010free survival (PFS) in excess of 5\u00a0years in Waldenstr\u00f6m macroglobulinaemia (WM) patients. <jats:italic>CXCR4<\/jats:italic> mutations are detected in 30\u201340% of patients with WM and associate with lower rates of response and shorter PFS to ibrutinib therapy. Both frameshift (<jats:italic>CXCR4<\/jats:italic><jats:sup>FS<\/jats:sup>) and nonsense (<jats:italic>CXCR4<\/jats:italic><jats:sup>NS<\/jats:sup>) <jats:italic>CXCR4<\/jats:italic> mutations have been described. The impact of these mutations on outcomes to ibrutinib have not been evaluated in WM patients. We studied consecutive patients with a diagnosis of WM, on ibrutinib therapy, for the presence of <jats:italic>CXCR4<\/jats:italic><jats:sup>FS<\/jats:sup> and <jats:italic>CXCR4<\/jats:italic><jats:sup>NS<\/jats:sup> mutations and evaluated the differences in response and PFS between groups. Of 180 patients, 68 patients (38%) had <jats:italic>CXCR4<\/jats:italic> mutations; 49 (27%) had <jats:italic>CXCR4<\/jats:italic><jats:sup>NS<\/jats:sup> and 19 (11%) had <jats:italic>CXCR4<\/jats:italic><jats:sup>FS<\/jats:sup> mutations. In multivariate models, patients with <jats:italic>CXCR4<\/jats:italic><jats:sup>NS<\/jats:sup> had lower odds of major response (Odds ratio 0\u00b725, 95% confidence interval [CI] 0\u00b712\u20130\u00b753; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) and worse PFS (Hazard ratio 4\u00b702, 95% CI 1\u00b795\u20138\u00b726; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) than patients without <jats:italic>CXCR4<\/jats:italic> mutations. <jats:italic>CXCR4<\/jats:italic><jats:sup>FS<\/jats:sup> was not associated with worse major response or PFS rates than patients without <jats:italic>CXCR4<\/jats:italic> mutations. Our results suggest different response and PFS rates to ibrutinib for WM patients with <jats:italic>CXCR4<\/jats:italic><jats:sup>NS<\/jats:sup> and <jats:italic>CXCR4<\/jats:italic><jats:sup>FS<\/jats:sup>, and advocate in favour of <jats:italic>CXCR4<\/jats:italic> mutational testing as well as <jats:italic>CXCR4<\/jats:italic>\u2010directed therapy.<\/jats:p>","DOI":"10.1111\/bjh.16088","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T07:45:00Z","timestamp":1562139900000},"page":"356-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["<i>CXCR4<\/i> mutation subtypes impact response and survival outcomes in patients with Waldenstr\u00f6m macroglobulinaemia treated with ibrutinib"],"prefix":"10.1111","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-7532","authenticated-orcid":false,"given":"Jorge 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Guerrera","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria G.","family":"Chan","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute Boston MA USA"},{"name":"Department of 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