{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:32:23Z","timestamp":1791995543530,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014491","name":"Pharmacyclics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The BTK inhibitor ibrutinib and the BCL\u20102 antagonist venetoclax are active therapies as single agents in Waldenstr\u00f6m macroglobulinemia (WM). In this phase 2 study, we sought to investigate the combination of ibrutinib and venetoclax as a 2\u2010year fixed\u2010duration, oral\u2010based, chemotherapy\u2010free regimen in symptomatic, treatment\u2010naive WM patients. All patients had\n                    <jats:italic>MYD88<\/jats:italic>\n                    mutations, 17 (38%) had\n                    <jats:italic>CXCR4<\/jats:italic>\n                    mutations, and 4 (9%) had\n                    <jats:italic>TP53<\/jats:italic>\n                    alterations. Following enrollment of 45 patients, treatment and enrollment were stopped due to the occurrence of ventricular arrhythmias in 4 (9%), which included two grade 5 events. The median treatment time was 10\u2009cycles, each lasting 28\u2009days. Follow\u2010up continued after protocol treatment was terminated. The very good partial response\/complete response (VGPR\/CR) rate was 42%, and it was lower in patients with\u00a0\n                    <jats:italic>CXCR4<\/jats:italic>\n                    (29% vs. 50%) or\n                    <jats:italic>TP53<\/jats:italic>\n                    (25% vs. 44%) mutations. With a median follow\u2010up of 49\u2009months, the median progression\u2010free survival (PFS) was 36\u2009months (range 28\u201342). The median treatment\u2010free survival (TFS) and overall survival (OS) were\u00a0not reached, and the 4\u2010year TFS and OS rates were 73% and 91%, respectively. The median PFS after end of therapy (PFS\u2010EOT) was 29\u2009months.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations were associated with inferior PFS, TFS, and PFS\u2010EOT, while\n                    <jats:italic>CXCR4<\/jats:italic>\n                    mutations did not adversely impact these outcomes. Given the deep and durable responses seen in this study, concurrent BTK and BCL\u20102 inhibition warrants further development in WM.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations emerged as an adverse factor in WM in this combination study.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70285","type":"journal-article","created":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T09:30:08Z","timestamp":1773567008000},"page":"1255-1263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Final Report of a Phase\n                    <scp>II<\/scp>\n                    Study of Ibrutinib and Venetoclax in Previously Untreated Waldenstr\u00f6m Macroglobulinemia"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-7532","authenticated-orcid":false,"given":"Jorge J.","family":"Castillo","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3868-9267","authenticated-orcid":false,"given":"Andrew R.","family":"Branagan","sequence":"additional","affiliation":[{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Multiple Myeloma, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-6643","authenticated-orcid":false,"given":"Alberto","family":"Guijosa","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts 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for Waldenstr\u00f6m Macroglobulinemia, Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Kofides","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-9134","authenticated-orcid":false,"given":"Shirong","family":"Liu","sequence":"additional","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":"Xia","family":"Liu","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana\u2010Farber Cancer Institute  Boston 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