{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:18:14Z","timestamp":1790731094685,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>We conducted this first systematic review and meta-analysis to assess the competitive advantage of 2nd-generation Bruton tyrosine kinase inhibitors (BTKi) compared to 1st-generation BTKi in chronic lymphocytic leukemia (CLL). The literature search was conducted from PubMed, Web of Science, Embase databases, and hematology annual conferences. Data of over response rate (ORR), progression-free survival (PFS), and overall survival (OS) were extracted to a pool meta-analysis of efficacy; adverse events (AEs) were also extracted to a pool meta-analysis of safety. Bias risk assessment and meta-analysis were performed by Review Manager 5.3 and STATA 14 software. A total of 3649 patients from 29 cohorts were included. The results showed that the benefits of ORR and 24-month PFS in 2nd-generation BTKi compared to 1st-generation BTKi were not significant in the whole population but only in the relapsed or refractory (R\/R) CLL patient subgroup (ORR: 86.4% vs. 76.2%, <jats:italic>p<\/jats:italic> = 0.013; 24-month PFS: 76.9% vs. 67.9%, <jats:italic>p<\/jats:italic> = 0.004). Any-grade AEs were comparable between 1st- and 2nd-generation BTKi, but grade 3 or higher AEs were significantly less frequent with 2nd-generation BTKi <jats:italic>versus<\/jats:italic> 1st-generation BTKi (grade 3 or higher: 53.1% vs. 72.5%; <jats:italic>p<\/jats:italic> = 0.002). Headache was more frequent with 2nd-generation BTKi, while diarrhea and atrial fibrillation were more frequent with 1st-generation BTKi. Only for patients with relapsed or refractory CLL did 2nd-generation BTKi have a competitive advantage, while adverse effects still need to be considered.<\/jats:p><jats:p><jats:bold>Systematic Review Registration:<\/jats:bold><jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO<\/jats:ext-link>, Identifier 42022342488.<\/jats:p>","DOI":"10.3389\/fphar.2024.1413985","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T05:10:15Z","timestamp":1720588215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and safety of first- versus second-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Liyuan","family":"Ke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danxue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1002\/ajh.26552","article-title":"First-versus second-generation Bruton tyrosine kinase inhibitors in Waldenstr\u00f6m's Macroglobulinemia: a systematic review and meta-analysis","volume":"97","author":"Abushukair","year":"2022","journal-title":"Am. 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