{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:16:38Z","timestamp":1792818998066,"version":"4.5.0"},"reference-count":48,"publisher":"American Society of Hematology","issue":"7","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,15]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Concurrent Bruton tyrosine kinase and BCL2 inhibition has not yet been investigated in Waldenstr\u00f6m macroglobulinemia (WM). We performed an investigator-initiated trial of ibrutinib and venetoclax in symptomatic treatment-na\u00efve patients with MYD88-mutated WM. Patients received ibrutinib 420 mg once daily (cycle 1), followed by a ramp-up of venetoclax to 400 mg daily (cycle 2). The combination was then administered for 22 additional 4-week cycles. The attainment of very good partial response (VGPR) was the primary end point. Forty-five patients were enrolled in this study. The median baseline characteristics were as follows: age 67 years, serum IgM 43 g\/L, and hemoglobin 102 g\/L. Seventeen patients (38%) carried CXCR4 mutations. Nineteen patients (42%) achieved VGPR. Grade 3 or higher adverse events included neutropenia (38%), mucositis (9%), and tumor lysis syndrome (7%). Atrial fibrillation occurred in 3 (9%), and ventricular arrhythmia in 4 (9%) patients that included 2 grade 5 events. With a median follow-up of 24.4 months, the 24-month progression-free survival (PFS) and overall survival (OS) rates were 76% and 96%, respectively, and were not impacted by CXCR4 mutations. The median time on therapy was 10.2 months, and the median time after the end of therapy (EOT) was 13.3 months. Eleven of the 12 progression events occurred after EOT, and the 12-month PFS rates after EOT were 79%; 93% if VGPR was attained, and 69% for other patients (P = .12). Ibrutinib and venetoclax induced high VGPR rates and durable responses after EOT, although they were associated with a higher-than-expected rate of ventricular arrhythmia in patients with WM, leading to early study treatment termination. This trial was registered at www.clinicaltrials.gov as #NCT04273139.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023022420","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T13:30:37Z","timestamp":1700141437000},"page":"582-591","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":29,"title":["Ibrutinib and venetoclax as primary therapy in symptomatic, treatment-na\u00efve Waldenstr\u00f6m macroglobulinemia"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-7532","authenticated-orcid":false,"given":"Jorge J.","family":"Castillo","sequence":"first","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"},{"name":"2Department of Medicine, Harvard Medical School, Boston, MA"}],"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":"2Department of Medicine, Harvard Medical School, Boston, MA"},{"name":"3Center for Multiple Myeloma, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-7728","authenticated-orcid":false,"given":"David","family":"Sermer","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Harvard Medical School, Boston, MA"},{"name":"4Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Flynn","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Meid","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Little","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Stockman","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"White","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Canning","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-4678","authenticated-orcid":false,"given":"Maria L.","family":"Guerrera","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Kofides","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirong","family":"Liu","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer 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MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1689-1691","authenticated-orcid":false,"given":"Zachary R.","family":"Hunter","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6393-6154","authenticated-orcid":false,"given":"Steven P.","family":"Treon","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA"},{"name":"2Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-6735","authenticated-orcid":false,"given":"Shayna","family":"Sarosiek","sequence":"additional","affiliation":[{"name":"1Bing Center for Waldenstr\u00f6m Macroglobulinemia, Dana-Farber Cancer 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