{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T06:42:17Z","timestamp":1740120137799,"version":"3.37.3"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Janssen Pharmaceutical K.K., Tokyo, Japan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ibrutinib is a first-in-class Bruton kinase inhibitor against B-cell neoplasms including Waldenstr\u00f6m macroglobulinemia (WM). This study evaluated the efficacy and safety of ibrutinib-rituximab in Japanese patients with WM. Patients received ibrutinib 420\u00a0mg orally once daily plus weekly rituximab 375\u00a0mg\/m<jats:sup>2<\/jats:sup> IV (8 infusions total). The primary end point was major response rate (MRR; PR or better) by Independent Review Committee assessment. Secondary endpoints were progression-free survival (PFS), safety, pharmacokinetics, and biomarkers. Primary analysis was conducted in 16 patients [baseline, treatment na\u00efve: 8 (50.0%); relapsed\/refractory WM: 8 (50.0%)] who received ibrutinib-rituximab, after all patients completed Week 57 or end of treatment. At primary analysis, MRR was 87.5% [14\/16 patients; 95% CI: 61.7, 98.4%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001 (null hypothesis: 32% response rate)]. At final analysis (median study intervention duration: 34.4\u00a0months, median follow-up: 35.0\u00a0months), MRR was unchanged at 87.5%, but VGPR [6\/16 (37.5%)] and PR [8\/16 (50.0%)] improved. Prior treatment status did not affect response. At final analysis, median PFS was not reached [36-month PFS rate: 86% (95% CI: 55, 96%)]. No critical safety signals were reported. This study demonstrated a positive benefit\/risk profile of ibrutinib-rituximab in Japanese patients with WM, consistent with the iNNOVATE study.<\/jats:p>","DOI":"10.1007\/s12185-024-03761-9","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T15:02:00Z","timestamp":1712761320000},"page":"80-90","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase 2, open-label study of ibrutinib plus rituximab in Japanese patients with Waldenstrom\u2019s macroglobulinemia"],"prefix":"10.1007","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8057","authenticated-orcid":false,"given":"Koji","family":"Izutsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Sekiguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Fujisaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiro","family":"Kawakita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoshi","family":"Obara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosei","family":"Matsue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsutaka","family":"Nishimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyoshi","family":"Hatayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuo","family":"Inagaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ei","family":"Fujikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"issue":"2","key":"3761_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1053\/j.seminhematol.2023.03.008","volume":"60","author":"ML McMaster","year":"2023","unstructured":"McMaster ML. 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Hisashi Kato received lecture fees from Janssen Pharmaceutical. Naohiro Sekiguchi received research funding from Janssen, Astellas, Ono, Incyte Biosciences Japan, Merck Sharp & Dohme, Otsuka, Pfizer. Kosei Matsue received research grant from ASZ. Mitsutaka Nishimoto received research funding from Janssen Pharma. Tomoaki Fujisaki, Toshiro Kawakita, and Naoshi Obara has nothing to disclose. Tomoyoshi Hatayama, Mitsuo Inagaki, and Ei Fujikawa are employees of Janssen Pharmaceutical K.K., Tokyo, Japan and holds stocks of Johnson & Johnson.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}