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This review summarizes the recent data strongly suggesting a role for the integration of covalent BTK inhibition in the first-line treatment setting, after the recent presentation and publication of multiple phase II and randomized phase II\/III clinical trials demonstrating benefit for the addition of cBTK inhibitors first line. The authors discuss herein the strength and quality of the evidence for therapeutic strategies integrating cBTK inhibitors first line and proposal treatment algorithms on the basis of assumed future availability of this highly active small molecules first line in the near future.<\/jats:p>","DOI":"10.1200\/jco-25-00146","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T19:59:23Z","timestamp":1748548763000},"page":"2300-2310","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Mantle Cell Lymphoma: Optimal Treatment With Bruton Tyrosine Kinase\u2013Targeted Approaches"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-9749","authenticated-orcid":true,"given":"Toby A.","family":"Eyre","sequence":"first","affiliation":[{"name":"Oxford Haematology and Cancer Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Churchill Drive, 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