{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:35:39Z","timestamp":1791498939173,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mantle Cell Lymphoma (MCL) is an aggressive B\u2010cell non\u2010Hodgkin lymphoma characterized by the hallmark t(11;14)(q13;q32) translocation, resulting in cyclin D1 overexpression. Predominantly affecting elderly males, MCL exhibits marked clinical and biological heterogeneity, ranging from indolent SOX11\u2010negative variants to highly proliferative blastoid variants. Despite initial responsiveness to chemoimmunotherapy, relapse is frequent, and median overall survival remains limited. Aberrant B\u2010cell receptor (BCR) signaling\u2014mediated by kinases including Bruton's tyrosine kinase (BTK)\u2014plays a central role in MCL pathogenesis. BTK inhibitors (BTKis) such as ibrutinib (as monotherapy or combined with R\u2010CHOP\/R\u2010DHAP), acalabrutinib (with rituximab and bendamustine), and pirtobrutinib have significantly improved outcomes of relapsed\/refractory disease. However, their efficacy is challenged by resistance mutations (e.g., BTK C481S) and off\u2010target toxicities. Next\u2010generation reversible BTKis represent an important advance, offering activity in the setting of resistance and improved tolerability. Resistance is further sustained by the tumor microenvironment through stromal support and immunosuppressive cellular interactions. Consequently, combination strategies incorporating BTKis with BCL\u20102 inhibitors, monoclonal antibodies, and cellular therapies are being investigated to enhance response depth and durability. In parallel, biomarker\u2010driven approaches and precision\u2010medicine strategies are emerging to personalize disease monitoring and treatment selection. Collectively, these developments underscore the evolving role of BTK inhibition within broader immune\u2010based and targeted treatment paradigms in MCL.<\/jats:p>","DOI":"10.1111\/ejh.70036","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T08:49:54Z","timestamp":1757753394000},"page":"599-609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bruton Tyrosine Kinase Inhibitors in Mantle Cell Lymphoma: What Are the Current Options?"],"prefix":"10.1111","volume":"115","author":[{"given":"Santino","family":"Caserta","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica Antonia","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza 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