{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:19:09Z","timestamp":1787019549001,"version":"build-2736575974"},"reference-count":44,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed\/refractory MCL and penetrates the blood\u2013brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n\u00a0= 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate\u00a0\u00b1 cytarabine; n\u00a0= 29, BBB cohort), or miscellaneous treatments (n\u00a0= 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P\u00a0= .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P\u00a0= .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P\u00a0&amp;lt; .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P\u00a0= .002), followed by CNS progression of disease (POD) &amp;gt;24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P\u00a0= .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P\u00a0= .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P\u00a0= .502) as the morphological variant (classical vs others, P\u00a0= .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.<\/jats:p>","DOI":"10.1182\/blood.2022015560","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T16:11:51Z","timestamp":1657037511000},"page":"1907-1916","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":47,"title":["Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse"],"prefix":"10.1182","volume":"140","author":[{"given":"Chiara","family":"Rusconi","sequence":"first","affiliation":[{"name":"1Division of Hematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7988-1565","authenticated-orcid":false,"given":"Chan Y.","family":"Cheah","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Sir Charles Gairdner Hospital, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-9749","authenticated-orcid":false,"given":"Toby A.","family":"Eyre","sequence":"additional","affiliation":[{"name":"3Oxford University Hospitals, NHS Foundation Trust, Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Tucker","sequence":"additional","affiliation":[{"name":"4Department of Haematology, Royal Cornwall Hospital NHS Trust, Truro, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-9378","authenticated-orcid":false,"given":"Pavel","family":"Klener","sequence":"additional","affiliation":[{"name":"5First Department of Internal Medicine-Hematology, General University Hospital in Prague and First Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Gin\u00e9","sequence":"additional","affiliation":[{"name":"6Hematology Department, Hospital Cl\u00ednic, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Crucitti","sequence":"additional","affiliation":[{"name":"7Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-3222","authenticated-orcid":false,"given":"Cristina","family":"Muzi","sequence":"additional","affiliation":[{"name":"7Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Iadecola","sequence":"additional","affiliation":[{"name":"8Unit of Clinical Epidemiology and Trial Organization, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-5784","authenticated-orcid":false,"given":"Gabriele","family":"Infante","sequence":"additional","affiliation":[{"name":"9Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Bernard","sequence":"additional","affiliation":[{"name":"10APHP, Saint-Louis Hospital, Hemato-oncology Department, Paris & University of Paris, Diderot University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Auer","sequence":"additional","affiliation":[{"name":"11Centre for Haemato-Oncology, St.Bartholomew\u2019s Hospital Barts Health NHS Trust, London, United 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Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Cencini","sequence":"additional","affiliation":[{"name":"16U.O.C. Ematologia, Ospedale Policlinico Santa Maria alle Scotte, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Marin-Niebla","sequence":"additional","affiliation":[{"name":"17Hematology Department, Vall d\u2019Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Williams","sequence":"additional","affiliation":[{"name":"18Hematology\/Oncology Division, University of Virginia Cancer Center, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piera","family":"Angelillo","sequence":"additional","affiliation":[{"name":"19Lymphoma Unit Department of OncoHematology San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Nicoli","sequence":"additional","affiliation":[{"name":"20SCDU Medicina Interna a Indirizzo Ematologico, AOU San Luigi Gonzaga, Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Arcari","sequence":"additional","affiliation":[{"name":"21Haematology and Bone Marrow Transplant Unit, \u201cGuglielmo da Saliceto\u201d Hospital, Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Morello","sequence":"additional","affiliation":[{"name":"22Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1258","authenticated-orcid":false,"given":"Donato","family":"Mannina","sequence":"additional","affiliation":[{"name":"23UOC di Ematologia, Azienda Ospedaliera Papardo, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsola","family":"Vitagliano","sequence":"additional","affiliation":[{"name":"24Division of Hematology, Cardarelli Hospital, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Sartori","sequence":"additional","affiliation":[{"name":"25Onco Hematology Unit, Istituto Oncologico Veneto IOV-IRCSS, Castelfranco Veneto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-0098","authenticated-orcid":false,"given":"Annalisa","family":"Chiappella","sequence":"additional","affiliation":[{"name":"26Division of Hematology, A.O. 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