{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:02:22Z","timestamp":1789578142627,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Waldenstr\u00f6m macroglobulinaemia (WM) is characterized by the presence of a <jats:italic>MYD88<\/jats:italic><jats:sup>L265P<\/jats:sup> mutation. This mutation promotes growth and survival of malignant cells through Bruton tyrosine kinase (BTK) activation. Ibrutinib was the first BTK inhibitor approved for WM. Intolerance to ibrutinib frequently leads to dose reductions, though the impact of reducing ibrutinib dosing has not been systematically studied. We performed a retrospective study to determine the frequency and impact of reducing ibrutinib dosing in WM patients. With a median treatment time of 64\u2009months, 96 (27%) of 353 WM patients required a dose reduction due to adverse events such as musculoskeletal symptoms, cardiac events, dermatologic symptoms, cytopenias, and gastrointestinal symptoms. The median time to initial dose reduction was 9.3\u00a0months (range, 0.5\u201374). Dose reductions were more common in those 65\u2009years of age or older versus under 65 [hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.55\u20133.90; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001], and in females versus males (HR 2.20, 95% CI 1.41\u20133.28, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Most patients (65%) had improvement or resolution of adverse effects after initial dose reduction. With a median follow\u2010up of three years from dose reduction, hematologic response sustained or deepened in 79% of patients. These data suggest that dose reduction of ibrutinib is a reasonable treatment approach for patients with intolerable side effects.<\/jats:p>","DOI":"10.1111\/bjh.18643","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T23:54:29Z","timestamp":1673394869000},"page":"897-904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Dose reductions in patients with Waldenstr\u00f6m macroglobulinaemia treated with ibrutinib"],"prefix":"10.1111","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-6735","authenticated-orcid":false,"given":"Shayna","family":"Sarosiek","sequence":"first","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua N.","family":"Gustine","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Flynn","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly","family":"Leventoff","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Little","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia Dana\u2010Farber Cancer 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