{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:46:44Z","timestamp":1762868804924,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenstr\u00f6m's macroglobulinemia (WM). Whether second\u2010generation BTKi are associated with improved outcomes and\/or better safety profile remains unclear. We did a systematic review and meta\u2010analysis of clinical trials that reported data on the outcomes of patients with WM who received either first\u2010 or second\u2010generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis (<jats:italic>n<\/jats:italic>\u00a0=\u2009730 patients). A total of 298 patients received 1st\u2010generation BTKi and 432 received a 2nd\u2010generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut\/CXCR4 WT patients compared to MYD88 Mut\/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18\u2010mo progression\u2010free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3\/4 atrial fibrillation was higher in 1st\u2010generation BTKi (3.1% vs. 0.4%); however, grade\u20103\/\u20104 infections and neutropenia were more frequent in 2nd\u2010generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st\u2010 and 2nd\u2010generation BTKis is comparable. The 1st\u2010generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd\u2010generation BTKi.<\/jats:p>","DOI":"10.1002\/ajh.26552","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T18:05:21Z","timestamp":1648749921000},"page":"942-950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["First\u2010 versus second\u2010generation Bruton tyrosine kinase inhibitors in Waldenstr\u00f6m's Macroglobulinemia: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0068-5201","authenticated-orcid":false,"given":"Hassan","family":"Abushukair","sequence":"first","affiliation":[{"name":"Faculty of Medicine Jordan University of Science and Technology  Irbid Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebawe","family":"Syaj","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Jordan University of Science and Technology  Irbid Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-9095","authenticated-orcid":false,"given":"Obada","family":"Ababneh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Jordan University of Science and Technology  Irbid Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aref","family":"Qarqash","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Jordan University of Science and Technology  Irbid Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2699-1741","authenticated-orcid":false,"given":"Carolina","family":"Schinke","sequence":"additional","affiliation":[{"name":"Myeloma Center Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-411X","authenticated-orcid":false,"given":"Sharmilan","family":"Thanendrarajan","sequence":"additional","affiliation":[{"name":"Myeloma Center Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1720-3854","authenticated-orcid":false,"given":"Maurizio","family":"Zangari","sequence":"additional","affiliation":[{"name":"Myeloma Center Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-1282","authenticated-orcid":false,"given":"Frits","family":"van Rhee","sequence":"additional","affiliation":[{"name":"Myeloma Center Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-8042","authenticated-orcid":false,"given":"Samer","family":"Al Hadidi","sequence":"additional","affiliation":[{"name":"Myeloma Center Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2003.50064"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26082"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","unstructured":"DimopoulosMA TrotmanJ TedeschiA et al.Articles Ibrutinib for Patients with Rituximab\u2010Refractory Waldenstr\u00f6m's Macro Globulinaemia (iNNOVATE): an Open\u2010Label Substudy of an International Multicentre Phase 3 Trial.2016;","DOI":"10.1016\/S1470-2045(16)30632-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201001\u2010550905"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501548"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2018.05.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2015-2597"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006844"},{"key":"e_1_2_9_10_1","unstructured":"US FDA.FDA Approves Zanubrutinib for Waldenstr\u00f6m's Macroglobulinemia.2021. 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