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However, primary and acquired resistance to BTKi can be seen due to a variety of mechanisms including tumour intrinsic and extrinsic mechanisms such as gene mutations, activation of bypass signalling pathways and tumour microenvironment. Herein, we provide an updated review of the key clinical data of BTKi treatment in CLL, mantle cell lymphoma, and diffuse large B\u2010cell lymphoma (DLBCL). We incorporate the most recent findings regarding mechanisms of resistance to covalent and non\u2010covalent inhibitors, including ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib. We also cover the clinical sensitivity of certain molecular subtypes of DLBCL to an ibrutinib\u2010containing regimen. Lastly, we summarise ongoing clinical investigations aimed at overcoming resistance via use of BTKi\u2010containing combined therapies or the novel non\u2010covalent BTKi. The review article targets an audience of clinical practitioners, clinical investigators and translational researchers.<\/jats:p>","DOI":"10.1111\/bjh.18418","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T06:00:58Z","timestamp":1661580058000},"page":"137-149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Resistance to\n                    <scp>Bruton tyrosine kinase<\/scp>\n                    inhibition in\n                    <scp>chronic lymphocytic leukaemia<\/scp>\n                    and\n                    <scp>non\u2010Hodgkin<\/scp>\n                    lymphoma"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-8860","authenticated-orcid":false,"given":"Shazia","family":"Nakhoda","sequence":"first","affiliation":[{"name":"Department of Hematology Fox Chase Cancer Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldana","family":"Vistarop","sequence":"additional","affiliation":[{"name":"Department of Pathology Fox Chase Cancer Center  Philadelphia Pennsylvania USA"},{"name":"Blood Cell Development and Function Program Fox Chase Cancer Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0773-1212","authenticated-orcid":false,"given":"Y. 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