{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:02:34Z","timestamp":1760148154714,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the EMPIRIS foundation in Zurich, Switzerland","award":["TP, 003-17"],"award-info":[{"award-number":["TP, 003-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Background: First-line therapy in fit MCL patients may comprise high-dose chemotherapy (HDCT) with autologous transplantation to consolidate remission before maintenance treatment. However, optimization of HDCT is an unmet clinical need given the substantial relapse rate of first-line treatment, while the use of bortezomib is a promising candidate to be added to standard HDCT. (2) Methods: We analyzed 11 consecutive patients with MCL who received bortezomib added to standard BeEAM (2BeEAM) HDCT at a single academic institution. We assessed safety, feasibility, toxicities, and survival rates. (3) Results: All patients had stage III or IV disease. We found that six patients (55%) developed new or worsening of preexisting peripheral neuropathy following administration of 2BeEAM HDCT. One patient relapsed within the first six months after HDCT, whereas three patients never reached complete remission. After a median follow-up of 22 months, the PFS was 64% and the OS 64% at the last follow-up assessment. At this time, 55% of patients were in CR. (4) Conclusions: The use of bortezomib added to standard BeEAM HDCT is associated with relevant toxicities, particularly with regards to additional neuropathy. Moreover, the anti-lymphoma efficacy of 2BeEAM HDCT appears to be modest; therefore, other therapeutic options should be evaluated for consolidation in this patient group.<\/jats:p>","DOI":"10.3390\/cancers15072091","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T02:30:20Z","timestamp":1680229820000},"page":"2091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Bortezomib-BeEAM (2BeEAM) as Chemotherapy Regimen Prior to ASCT in Patients with Mantle Cell Lymphoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Fabrizio","family":"Huwyler","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekka","family":"Kunz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-947X","authenticated-orcid":false,"given":"Ulrike","family":"Bacher","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mich\u00e8le","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7642-2101","authenticated-orcid":false,"given":"Urban","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8138-0505","authenticated-orcid":false,"given":"Michael","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yara","family":"Banz","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Inselspital, University of Bern, 3008 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-5257","authenticated-orcid":false,"given":"Thomas","family":"Pabst","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"iv62","DOI":"10.1093\/annonc\/mdx223","article-title":"Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Dreyling","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/ajh.24797","article-title":"Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management","volume":"92","author":"Vose","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1182\/blood-2009-02-179739","article-title":"How I treat mantle cell lymphoma","volume":"114","author":"Ghielmini","year":"2009","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1182\/blood.V116.21.110.110","article-title":"Alternating Courses of 3x CHOP and 3x DHAP Plus Rituximab Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation (ASCT) Is Superior to 6 Courses CHOP Plus Rituximab Followed by Myeloablative Radiochemotherapy and ASCT In Mantle Cell Lymphoma: Results of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net)","volume":"116","author":"Hermine","year":"2010","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6101","DOI":"10.1200\/JCO.2009.22.2554","article-title":"Immunochemotherapy and Autologous Stem-Cell Transplantation for Untreated Patients With Mantle-Cell Lymphoma: CALGB 59909","volume":"27","author":"Damon","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/hon.2952","article-title":"Outcome of patients with mantle cell lymphoma after autologous stem cell transplantation in the pre-CAR T-cell era","volume":"40","author":"Mathys","year":"2021","journal-title":"Hematol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1182\/blood.V128.22.4648.4648","article-title":"BEAM or BeEAM High-Dose Chemotherapy Followed By ASCT: A Single Center Comparative Analysis of Toxicity","volume":"128","author":"Ribrag","year":"2016","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/s41409-020-0783-y","article-title":"Bendamustine-EAM versus BEAM regimen in patients with mantle cell lymphoma undergoing autologous stem cell transplantation in the frontline setting: A multicenter retrospective study from Lymphoma Study Association (LYSA) centers","volume":"55","author":"Hueso","year":"2020","journal-title":"Bone Marrow Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/hon.2197","article-title":"Zevalin and BEAM (Z-BEAM) versus rituximab and BEAM (R-BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma","volume":"34","author":"Berger","year":"2015","journal-title":"Hematol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/annonc\/mdl316","article-title":"A phase II study of bortezomib in mantle cell lymphoma: The National Cancer Institute of Canada Clinical Trials Group trial IND.150","volume":"18","author":"Belch","year":"2006","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1200\/JCO.2006.07.9665","article-title":"Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma","volume":"24","author":"Fisher","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_12","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_13","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_14","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/ajh.25783","article-title":"Bortezomib consolidation or maintenance following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma: CALGB \/Alliance 50403","volume":"95","author":"Kaplan","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1038\/s41409-019-0508-2","article-title":"High incidence of reversible renal toxicity of dose-intensified bendamustine-based high-dose chemotherapy in lymphoma and myeloma patients","volume":"54","author":"Prediletto","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1056\/NEJM199512073332305","article-title":"Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin's Lymphoma","volume":"333","author":"Philip","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-019-0209-5","article-title":"Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: Progressive shortening in response duration and survival after each relapse","volume":"9","author":"Kumar","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.leukres.2015.03.004","article-title":"CD34+ selected versus unselected autologous stem cell transplantation in patients with advanced-stage mantle cell and diffuse large B-cell lymphoma","volume":"39","author":"Berger","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.bbmt.2015.02.005","article-title":"Impact of Conditioning Regimen on Outcomes for Patients with Lymphoma Undergoing High-Dose Therapy with Autologous Hematopoietic Cell Transplantation","volume":"21","author":"Chen","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.bbmt.2016.03.018","article-title":"Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes","volume":"22","author":"Flowers","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/bmt.2015.273","article-title":"Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: A retrospective study from the EBMT","volume":"51","author":"Sellner","year":"2015","journal-title":"Bone Marrow Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1182\/blood-2011-04-351924","article-title":"BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant\/relapsed lymphoma patients","volume":"118","author":"Visani","year":"2011","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1182\/blood-2014-08-596668","article-title":"Bendamustine, etoposide, cytarabine, melphalan, and autologous stem cell rescue produce a 72% 3-year PFS in resistant lymphoma","volume":"124","author":"Visani","year":"2014","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00277-016-2900-y","article-title":"BeEAM conditioning with bendamustine-replacing BCNU before autologous transplantation is safe and effective in lymphoma patients","volume":"96","author":"Gilli","year":"2016","journal-title":"Ann. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/bjh.13101","article-title":"Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma","volume":"168","author":"Furtado","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.bbmt.2014.01.004","article-title":"Phase I\/II Study of Bortezomib-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Relapsed Indolent Non-Hodgkin Lymphoma, Transformed, or Mantle Cell Lymphoma","volume":"20","author":"William","year":"2014","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1200\/JCO.2013.52.2466","article-title":"Confirmation of the Mantle-Cell Lymphoma International Prognostic Index in Randomized Trials of the European Mantle-Cell Lymphoma Network","volume":"32","author":"Hoster","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_28","unstructured":"U.S. Food and Drug Administration (FDA) (2020, July 24). FDA Approves First Cell-Based Gene Therapy for Adult Patients with Relapsed or Refractory MCL, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-cell-based-gene-therapy-adult-patients-relapsed-or-refractory-mcl."},{"key":"ref_29","unstructured":"European Medicines Agency (EMA) (2020, July 14). Tecartus (Autologous Anti-CD19-Transduced CD3+ Cells): An Overview of Tecartus and Why It Is Authorized in the EU. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/overview\/tecartus-epar-medicine-overview_en.pdf."},{"key":"ref_30","unstructured":"(2023, February 01). Schweizerisches Heilmittelinstitut Swissmedic. Tecartus, Infusionsdispersion (Autologe Anti-CD19-Transduzierte CD3+ Zellen). Available online: https:\/\/www.swissmedic.ch\/swissmedic\/de\/home\/humanarzneimittel\/authorisations\/new-medicines\/tecartus-infusiondispersion.html."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/s41409-022-01658-x","article-title":"Chimeric antigen receptor T-cell therapy for relapsed mantle cell lymphoma: Real-world experience from a single tertiary care center","volume":"57","author":"Heini","year":"2022","journal-title":"Bone Marrow Transplant."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/7\/2091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:07:56Z","timestamp":1760123276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/7\/2091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cancers15072091"],"URL":"https:\/\/doi.org\/10.3390\/cancers15072091","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2023,3,31]]}}}