{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:27:19Z","timestamp":1787225239649,"version":"build-2736575974"},"reference-count":90,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The introduction of Bruton\u2019s tyrosine kinase inhibitors (BTKis) has significantly improved prognosis in the treatment of MCL. BTK inhibitors have demonstrated strong activity in the treatment of relapsed\/refractory patients with mantle cell lymphoma (MCL), and several trials indicate that they also have potential as first-line treatment. Furthermore, combining BTKis with immunochemotherapy has enabled time-limited therapy as an alternative for continuous treatment with BTK inhibitors alone. In 2013, ibrutinib became the first BTK inhibitor to be approved by the FDA for previously treated MCL. The TRIANGLE study found ibrutinib to improve the efficacy of standard immunochemotherapy and reduce the need for autologous stem cell transplantation (ASCT) in younger patients; however, its findings do not conclusively confirm whether ASCT enhanced the activity of the ibrutinib-containing regimen in treatment-na\u00efve patients. The second-generation covalent, irreversible BTK inhibitors acalabrutinib and zanubrutinib demonstrate greater selectivity and better pharmacological characteristics than ibrutinib. The FDA has approved acalabrutinib and zanubrutinib as single drugs for the treatment of R\/R patients with MCL who have received at least one prior therapy. Acalabrutinib combined with bendamustine and rituximab was also approved for TN MCL unsuitable for ASCT. Pirtobrutinib, a first-in-class noncovalent reversible BTK inhibitor, was approved for the treatment of R\/R MCL patients, including those resistant to covalent BTK inhibitors. Several other covalent and noncovalent BTK inhibitors are currently under investigation in MCL. Finally, BTK degraders have entered early clinical trials in B-cell lymphoid malignancies, and some of them in MCL.<\/jats:p>","DOI":"10.3390\/cancers18162698","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:55:18Z","timestamp":1787223318000},"page":"2698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BTK Inhibitors for the Treatment of Mantle Cell Lymphoma\u2014Current Status and Perspectives"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-6357","authenticated-orcid":false,"given":"Tadeusz","family":"Robak","sequence":"first","affiliation":[{"name":"Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland"},{"name":"Department of General Hematology Internal Medicine, Copernicus Memorial Hospital, 93-510 Lodz,  Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-2098","authenticated-orcid":false,"given":"Anna","family":"Wolska-Washer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland"},{"name":"Department of Hematooncology and Internal Medicine, Copernicus Memorial Hospital, 93-510 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-5415","authenticated-orcid":false,"given":"Pawe\u0142","family":"Robak","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland"},{"name":"Department of Hematooncology and Internal Medicine, Copernicus Memorial Hospital, 93-510 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMra2202672","article-title":"Mantle-Cell Lymphoma","volume":"386","author":"Armitage","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70233","DOI":"10.1002\/hem3.70233","article-title":"EHA\u2013EU MCL Network Guidelines for Diagnosis and Treatment of Mantle Cell Lymphoma","volume":"9","author":"Jerkeman","year":"2025","journal-title":"HemaSphere"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/ajh.26523","article-title":"Mantle Cell Lymphoma in 2022\u2014A Comprehensive Update on Molecular Pathogenesis, Risk Stratification, Clinical Approach, and Current and Novel Treatments","volume":"97","author":"Jain","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/hon.3149","article-title":"Mantle Cell Lymphoma\u2014Update on Molecular Biology, Prognostication and Treatment Approaches","volume":"41","author":"Silkenstedt","year":"2023","journal-title":"Hematol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee","volume":"140","author":"Campo","year":"2022","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1182\/blood.2023022352","article-title":"Frontline Management of Mantle Cell Lymphoma","volume":"145","author":"Ryan","year":"2025","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1200\/JCO.2015.63.5904","article-title":"Mantle Cell Lymphoma","volume":"34","author":"Cheah","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.21037\/apm-22-345","article-title":"How to Treat Older Patients with Mantle Cell Lymphoma in the Era of Targeted Drugs","volume":"11","author":"Robak","year":"2022","journal-title":"Ann. Palliat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1200\/JCO.18.00605","article-title":"First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study","volume":"37","author":"Flinn","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1056\/NEJMoa1412096","article-title":"Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma","volume":"372","author":"Robak","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/S1470-2045(18)30685-5","article-title":"Frontline Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Transplantation-Ineligible Patients with Newly Diagnosed Mantle Cell Lymphoma: Final Overall Survival Results of a Randomised, Open-Label, Phase 3 Study","volume":"19","author":"Robak","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1470-2045(15)00559-8","article-title":"Lenalidomide versus Investigator\u2019s Choice in Relapsed or Refractory Mantle Cell Lymphoma (MCL-002; SPRINT): A Phase 2, Randomised, Multicentre Trial","volume":"17","author":"Lamy","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1182\/blood-2018-07-859769","article-title":"Five-Year Follow-up of Lenalidomide plus Rituximab as Initial Treatment of Mantle Cell Lymphoma","volume":"132","author":"Ruan","year":"2018","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1182\/blood-2016-03-704023","article-title":"Lenalidomide-Bendamustine-Rituximab in Patients Older than 65 Years with Untreated Mantle Cell Lymphoma","volume":"128","author":"Kolstad","year":"2016","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S1470-2045(12)70200-0","article-title":"Lenalidomide in Combination with Rituximab for Patients with Relapsed or Refractory Mantle-Cell Lymphoma: A Phase 1\/2 Clinical Trial","volume":"13","author":"Wang","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/ejh.70036","article-title":"Bruton Tyrosine Kinase Inhibitors in Mantle Cell Lymphoma: What Are the Current Options?","volume":"115","author":"Caserta","year":"2025","journal-title":"Eur. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Robak, T., Witkowska, M., and Smolewski, P. (2022). The Role of Bruton\u2019s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions. Cancers, 14.","DOI":"10.3390\/cancers14030771"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1080\/14656566.2026.2682839","article-title":"From Covalent to Reversible: The Expanding Role of BTK Inhibitors in Chronic Lymphocytic Leukemia","volume":"27","author":"Robak","year":"2026","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1200\/JCO-25-00146","article-title":"Mantle Cell Lymphoma: Optimal Treatment With Bruton Tyrosine Kinase\u2013Targeted Approaches","volume":"43","author":"Eyre","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.1200\/JCO.23.00562","article-title":"Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma","volume":"41","author":"Wang","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Salvaris, R.T., Brennan, J., and Lewis, K.L. (2025). BTK Is the Target That Keeps on Giving: A Review of BTK-Degrader Drug Development, Clinical Data, and Future Directions in CLL. Cancers, 17.","DOI":"10.3390\/cancers17030557"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/COC.0000000000001170","article-title":"Bruton Tyrosine Kinase Degraders: Current Concepts","volume":"48","author":"Sabakhtarishvili","year":"2025","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1007\/s00277-025-06515-7","article-title":"Next-Generation Bruton Tyrosine Kinase Inhibitors and Degraders in the Treatment of B-Cell Malignancies: Advances and Challenges","volume":"104","author":"Wang","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1182\/blood-2015-03-635326","article-title":"Long-Term Follow-up of MCL Patients Treated with Single-Agent Ibrutinib: Updated Safety and Efficacy Results","volume":"126","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"ref_25","unstructured":"Niu, T., Zhou, K., Zheng, Z., Li, F., Huang, H., Zhang, L., Su, L., Jing, H., Li, Z., and Zhang, X. (2025, January 10\u201314). Preliminary Safety and Efficacy of Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed\/Refractory B-Cell Malignancies: Results from CaDAnCe-102 (BGB-16673-102). Proceedings of the 2025 Annual Meeting of the Chinese Society of Clinical Oncology, Jinan, China. Available online: https:\/\/www.beonemedinfo.com\/CongressDocuments\/Niu_BGB-16673-102_CSCO_Abstract_2025.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(17)33108-2","article-title":"Acalabrutinib in Relapsed or Refractory Mantle Cell Lymphoma (ACE-LY-004): A Single-Arm, Multicentre, Phase 2 Trial","volume":"391","author":"Wang","year":"2018","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1200\/JCO-25-00690","article-title":"Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma","volume":"43","author":"Wang","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1182\/bloodadvances.2020004074","article-title":"Zanubrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma","volume":"5","author":"Tam","year":"2021","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1182\/bloodadvances.2022009168","article-title":"Orelabrutinib for the Treatment of Relapsed or Refractory MCL: A Phase 1\/2, Open-Label, Multicenter, Single-Arm Study","volume":"7","author":"Deng","year":"2023","journal-title":"Blood Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1182\/blood-2015-08-664086","article-title":"A Phase 1 Clinical Trial of the Selective BTK Inhibitor ONO\/GS-4059 in Relapsed and Refractory Mature B-Cell Malignancies","volume":"127","author":"Walter","year":"2016","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/ajh.26888","article-title":"DTRMWXHS-12, a Novel Bruton Tyrosine Kinase Inhibitor, in Combination with Everolimus and Pomalidomide in Patients with Relapsed\/Refractory Lymphomas: An Open-label, Multicenter, Phase 1a\/1b Study","volume":"98","author":"Huntington","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e7809236","DOI":"10.1097\/01.HS9.0000969416.78092.36","article-title":"P628: Updated analysis of BELLWAVE-001: A phase 1\/2 open-label dose-expansion study of the efficacy and safety of nemtabrutinib for the treatment of B-cell malignancies","volume":"7","author":"Woyach","year":"2023","journal-title":"HemaSphere"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1182\/blood-2024-205985","article-title":"Zilovertamab Vedotin in Combination with Nemtabrutinib for Patients with Relapsed or Refractory Mantle Cell Lymphoma: Cohort C of the Open-Label, Phase 2 Waveline-006 Study","volume":"144","author":"Moreira","year":"2024","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1021\/acs.biochem.8b00391","article-title":"Targeting the C481S Ibrutinib-Resistance Mutation in Bruton\u2019s Tyrosine Kinase Using PROTAC-Mediated Degradation","volume":"57","author":"Buhimschi","year":"2018","journal-title":"Biochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1056\/NEJMoa1306220","article-title":"Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma","volume":"369","author":"Wang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1182\/bloodadvances.2025017160","article-title":"Real-World Comparative Effectiveness of Bruton Tyrosine Kinase Inhibitors in Relapsed\/Refractory Mantle Cell Lymphoma","volume":"10","author":"Phillips","year":"2026","journal-title":"Blood Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1111\/cas.13076","article-title":"Efficacy and Safety of Ibrutinib in Japanese Patients with Relapsed or Refractory Mantle Cell Lymphoma","volume":"107","author":"Maruyama","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S1470-2045(15)00438-6","article-title":"Ibrutinib in Combination with Rituximab in Relapsed or Refractory Mantle Cell Lymphoma: A Single-Centre, Open-Label, Phase 2 Trial","volume":"17","author":"Wang","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/bjh.15411","article-title":"Four-year Follow-up of a Single Arm, Phase II Clinical Trial of Ibrutinib with Rituximab (IR) in Patients with Relapsed\/Refractory Mantle Cell Lymphoma (MCL)","volume":"182","author":"Jain","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1200\/JCO.21.01797","article-title":"Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma","volume":"40","author":"Jain","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1182\/bloodadvances.2023011152","article-title":"Ibrutinib as First-Line Therapy for Mantle Cell Lymphoma: A Multicenter, Real-World UK Study","volume":"8","author":"Tivey","year":"2024","journal-title":"Blood Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/S0140-6736(25)01432-1","article-title":"Ibrutinib and Rituximab versus Immunochemotherapy in Patients with Previously Untreated Mantle Cell Lymphoma (ENRICH): A Randomised, Open-Label, Phase 2\/3 Superiority Trial","volume":"406","author":"Lewis","year":"2025","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1056\/NEJMoa2201817","article-title":"Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma","volume":"386","author":"Wang","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0140-6736(15)00667-4","article-title":"Ibrutinib versus Temsirolimus in Patients with Relapsed or Refractory Mantle-Cell Lymphoma: An International, Randomised, Open-Label, Phase 3 Study","volume":"387","author":"Dreyling","year":"2016","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa1715519","article-title":"Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma","volume":"378","author":"Tam","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1182\/blood.2023023388","article-title":"Seven-Year Outcomes of Venetoclax-Ibrutinib Therapy in Mantle Cell Lymphoma: Durable Responses and Treatment-Free Remissions","volume":"144","author":"Handunnetti","year":"2024","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1182\/blood.2020008727","article-title":"Ibrutinib, Obinutuzumab, and Venetoclax in Relapsed and Untreated Patients with Mantle Cell Lymphoma: A Phase 1\/2 Trial","volume":"137","author":"Morschhauser","year":"2021","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/S2352-3026(18)30018-8","article-title":"Ibrutinib, Lenalidomide, and Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (PHILEMON): A Multicentre, Open-Label, Single-Arm, Phase 2 Trial","volume":"5","author":"Jerkeman","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e70101","DOI":"10.1002\/hem3.70101","article-title":"Ibrutinib, Lenalidomide, and Rituximab in Relapsed Mantle Cell Lymphoma: Long-term Follow-up of the Nordic Lymphoma Group MCL6 Philemon Trial","volume":"9","author":"Forsgren","year":"2025","journal-title":"HemaSphere"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/S0140-6736(24)00184-3","article-title":"Ibrutinib Combined with Immunochemotherapy with or without Autologous Stem-Cell Transplantation versus Immunochemotherapy and Autologous Stem-Cell Transplantation in Previously Untreated Patients with Mantle Cell Lymphoma (TRIANGLE): A Three-Arm, Randomised, Open-Label, Phase 3 Superiority Trial of the European Mantle Cell Lymphoma Network","volume":"403","author":"Dreyling","year":"2024","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1200\/JCO.21.02321","article-title":"Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial","volume":"40","author":"Terol","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/bjh.14870","article-title":"Outcomes in 370 Patients with Mantle Cell Lymphoma Treated with Ibrutinib: A Pooled Analysis from Three Open-label Studies","volume":"179","author":"Rule","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1080\/03007995.2024.2368175","article-title":"Overall Survival of Patients with CLL Treated with Ibrutinib in the First Line Compared to Second-Line Ibrutinib after Chemotherapy\/Chemoimmunotherapy","volume":"40","author":"Robak","year":"2024","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1158\/1078-0432.CCR-14-2225","article-title":"FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia","volume":"21","author":"McGinn","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s40199-022-00444-w","article-title":"Efficacy and Safety of Ibrutinib in Mantle Cell Lymphoma: A Systematic Review and Meta-Analysis","volume":"30","author":"Roufarshbaf","year":"2022","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/bjh.16922","article-title":"Treatment Patterns and Outcomes among Mantle Cell Lymphoma Patients Treated with Ibrutinib in the United States: A Retrospective Electronic Medical Record Database and Chart Review Study","volume":"192","author":"Sharman","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1080\/17460441.2026.2684645","article-title":"The preclinical discovery and development of acalabrutinib for the treatment of mantle cell lymphoma","volume":"21","author":"Robak","year":"2026","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_58","first-page":"343","article-title":"Final Results and Overall Survival Data from a Phase II Study of Acalabrutinib Monotherapy in Patients with Relapsed\/Refractory Mantle Cell Lymphoma, Including Those with Poor Prognostic Factors","volume":"109","author":"Gouill","year":"2024","journal-title":"Haematologica"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1038\/s41375-019-0575-9","article-title":"Durable Response with Single-Agent Acalabrutinib in Patients with Relapsed or Refractory Mantle Cell Lymphoma","volume":"33","author":"Wang","year":"2019","journal-title":"Leukemia"},{"key":"ref_60","first-page":"715","article-title":"Safety and Efficacy of Acalabrutinib plus Bendamustine and Rituximab in Patients with Treatment-Naive or Relapsed\/Refractory Mantle Cell Lymphoma: Phase Ib Trial","volume":"110","author":"Phillips","year":"2024","journal-title":"Haematologica"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1182\/bloodadvances.2023012424","article-title":"Acalabrutinib plus Venetoclax and Rituximab in Treatment-Naive Mantle Cell Lymphoma: 2-Year Safety and Efficacy Analysis","volume":"8","author":"Wang","year":"2024","journal-title":"Blood Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1182\/blood-2025-664","article-title":"Phase I\/II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in Patients with Relapsed\/Refractory and Previously Untreated Mantle Cell Lymphoma (MAVO)","volume":"146","author":"Kim","year":"2025","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1182\/bloodadvances.2025017760","article-title":"MRD-Driven Initial Therapy of Acalabrutinib and Lenalidomide plus Rituximab or Obinutuzumab for Mantle Cell Lymphoma","volume":"10","author":"Ruan","year":"2026","journal-title":"Blood Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1080\/17512433.2021.1978288","article-title":"Clinical Pharmacology and PK\/PD Translation of the Second-Generation Bruton\u2019s Tyrosine Kinase Inhibitor, Zanubrutinib","volume":"14","author":"Tam","year":"2021","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41408-023-00902-x","article-title":"Zanubrutinib: Past, Present, and Future","volume":"13","author":"Tam","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"388","author":"Brown","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.2020006844","article-title":"A Randomized Phase 3 Trial of Zanubrutinib vs Ibrutinib in Symptomatic Waldenstr\u00f6m Macroglobulinemia: The ASPEN Study","volume":"136","author":"Tam","year":"2020","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1182\/blood.2021014162","article-title":"Zanubrutinib in Relapsed\/Refractory Mantle Cell Lymphoma: Long-Term Efficacy and Safety Results from a Phase 2 Study","volume":"139","author":"Song","year":"2022","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2217\/fon-2020-0794","article-title":"A Phase III Study of Zanubrutinib Plus Rituximab Versus Bendamustine Plus Rituximab in Transplant-Ineligible, Untreated Mantle Cell Lymphoma","volume":"17","author":"Dreyling","year":"2021","journal-title":"Future Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1182\/blood.2024025563","article-title":"Zanubrutinib, Obinutuzumab, and Venetoclax for First-Line Treatment of Mantle Cell Lymphoma with a TP53 Mutation","volume":"145","author":"Kumar","year":"2025","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1111\/bjh.19419","article-title":"Safety and Efficacy of Zandelisib plus Zanubrutinib in Previously Treated Follicular and Mantle Cell Lymphomas","volume":"204","author":"Soumerai","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1080\/17460441.2023.2236547","article-title":"The Preclinical Discovery and Development of Orelabrutinib as a Novel Treatment Option for B-Cell Lymphoid Malignancies","volume":"18","author":"Robak","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood-2020-141781","article-title":"Long-Term Safety and Efficacy of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter, Open-Label, Phase II Study","volume":"136","author":"Song","year":"2020","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.2174\/0109298673251030231004052822","article-title":"Pirtobrutinib: First Non-Covalent Tyrosine Kinase Inhibitor forTreating Relapsed or Refractory Mantle Cell Lymphoma in Adults","volume":"31","author":"De","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_75","first-page":"62","article-title":"Pirtobrutinib Preclinical Characterization: A Highly Selective, Non-Covalent (Reversible) BTK Inhibitor","volume":"142","author":"Gomez","year":"2023","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S0140-6736(21)00224-5","article-title":"Pirtobrutinib in Relapsed or Refractory B-Cell Malignancies (BRUIN): A Phase 1\/2 Study","volume":"397","author":"Mato","year":"2021","journal-title":"Lancet"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1080\/03007995.2025.2607542","article-title":"Patient-Reported Outcomes among Patients with Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia Receiving Pirtobrutinib in the BRUIN Phase 1\/2 Study: Final Analysis","volume":"41","author":"Coombs","year":"2025","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1080\/10428194.2026.2621825","article-title":"Pirtobrutinib in Relapsed or Refractory Mantle Cell Lymphoma: Outcomes from the Compassionate Use Program in Italy","volume":"67","author":"Banegas","year":"2026","journal-title":"Leuk. Lymphoma"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e7289","DOI":"10.1002\/cam4.7289","article-title":"Outcomes of Pirtobrutinib for Relapsed\/Refractory Mantle Cell Lymphoma in Compassionate Use Program in Europe","volume":"13","author":"Aydilek","year":"2024","journal-title":"Cancer Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/s41375-019-0658-7","article-title":"Long-Term Follow-up of Patients with Mantle Cell Lymphoma (MCL) Treated with the Selective Bruton\u2019s Tyrosine Kinase Inhibitor Tirabrutinib (GS\/ONO-4059)","volume":"34","author":"Rule","year":"2020","journal-title":"Leukemia"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wang, J., Cheng, H., Sun, Y., Li, Z., Zang, Y., Zhao, Y., Yang, G., Liu, Z., Sun, Y., and Sun, Y. (2025). Efficacy and Safety of Tirabrutinib Monotherapy in Relapsed or Refractory B-Cell Lymphomas\/Leukemia: A Meta-Analysis. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1559056"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1182\/blood-2025-886","article-title":"Efficacy and Safety of Rocbrutinib, the Fourth Generation Bruton\u2019s Tyrosine Kinase Inhibitor, in Patients with BTK Inhibitor Pre-Treated Relapsed or Refractory Mantle Cell Lymphoma: Results from a Phase II Rock-1 Trial","volume":"146","author":"Song","year":"2025","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"C186","DOI":"10.1158\/1535-7163.TARG-15-C186","article-title":"Abstract C186: SNS-062 Is a Potent Noncovalent BTK Inhibitor with Comparable Activity against Wild Type BTK and BTK with an Acquired Resistance Mutation","volume":"14","author":"Binnerts","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"984","DOI":"10.3324\/haematol.2021.280061","article-title":"Phase Ib Dose-Escalation Study of the Selective, Non-Covalent, Reversible Bruton\u2019s Tyrosine Kinase Inhibitor Vecabrutinib in B-Cell Malignancies","volume":"107","author":"Allan","year":"2022","journal-title":"Haematologica"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Wolska-Washer, A., and Smolewski, P. (2022). Tar geting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies. Cancers, 14.","DOI":"10.3390\/cancers14153778"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1021\/acs.bioconjchem.6c00029","article-title":"Peptide-Based PROTACs: Transitioning from Static Paradigm to a Dynamic Landscape within Targeted Protein Degradation","volume":"37","author":"Lu","year":"2026","journal-title":"Bioconjugate Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1111\/bph.15014","article-title":"Proteolysis-targeting chimeras in drug development: A safety perspective","volume":"177","author":"Moreau","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1182\/blood-2022-164772","article-title":"NX-2127-001, a First-in-Human Trial of NX-2127, a Bruton\u2019s Tyrosine Kinase-Targeted Protein Degrader, in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and B-Cell Malignancies","volume":"140","author":"Mato","year":"2022","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1182\/blood-2025-85","article-title":"Updated Efficacy and Safety Results of the Bruton Tyrosine Kinase (BTK) Degrader BGB-16673 in Patients with Relapsed\/Refractory Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma (CLL\/SLL) from the Ongoing Phase 1 CaDAnCe-101 Study","volume":"146","author":"Ahn","year":"2025","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1182\/blood-2025-86","article-title":"Bexobrutideg (NX-5948), a Novel Bruton\u2019s Tyrosine Kinase (BTK) Degrader, Demonstrates Rapid and Durable Clinical Responses in Relapsed\/Refractory Chronic Lymphocytic Leukemia (CLL): New and Updated Findings from an Ongoing Phase 1a\/b Trial","volume":"146","author":"Omer","year":"2025","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2698\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:00:15Z","timestamp":1787223615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":90,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18162698"],"URL":"https:\/\/doi.org\/10.3390\/cancers18162698","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}