{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:52:20Z","timestamp":1793238740134,"version":"4.5.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009232","name":"University of Debrecen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009232","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Up to 30% of patients with classical Hodgkin lymphoma (cHL) are not responsive to frontline therapy or relapse after primary treatment. In these cases, autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care. The combination of brentuximab vedotin and bendamustine (BV\u2009+\u2009B) is an effective salvage regimen in this challenging subpopulation. This nationwide multicenter study investigated the real-world efficacy and safety of the BV\u2009+\u2009B regimen as a bridge to AHSCT in patients with primary refractory or relapsed cHL. A total of 41 cHL patients underwent AHSCT after receiving at least 1\u00a0cycle of BV\u2009+\u2009B (with brentuximab vedotin given at 1.8\u00a0mg\/kg on day 1 and bendamustine at 90\u00a0mg\/m<jats:sup>2<\/jats:sup> on days 1\u20132 every 4\u00a0weeks). After a median of 3 (1\u20136) cycles of BV\u2009+\u2009B, the objective response rate was 78%, with 29 (70.7%) patients achieving complete remission. Twelve (29.3%) patients relapsed after AHSCT, 2 (4.9%) of them died, while 2 (4.9%) patients are lost to follow-up. After a median of 17\u00a0months of follow-up, the estimated 2-year overall- and progression-free survival after AHSCT was 93 and 62%, respectively. Features of advanced disease at recurrence (<jats:italic>p<\/jats:italic>\u00a0=\u20090.038) and the presence of stage IV cHL at relapse (<jats:italic>p<\/jats:italic>\u00a0=\u20090.024) are strong predictor markers of unfavorable outcomes. Twenty-four (58.5%) patients experienced adverse events of any grade, while no grade IV toxicities were reported. BV\u2009+\u2009B is an effective salvage option with a manageable toxicity profile in cHL. The real-world safety and efficacy of this combination are similar to the observations made on the study population.<\/jats:p>","DOI":"10.1007\/s00277-020-04204-1","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T22:02:25Z","timestamp":1596492145000},"page":"2385-2392","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Real-world efficacy of brentuximab vedotin plus bendamustine as a bridge to autologous hematopoietic stem cell transplantation in primary refractory or relapsed classical Hodgkin lymphoma"],"prefix":"10.1007","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0453-1709","authenticated-orcid":false,"given":"L\u00e1szl\u00f3 Imre","family":"Pincz\u00e9s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rox\u00e1na","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1rp\u00e1d","family":"Ill\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"F\u00f6lde\u00e1k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kl\u00e1ra","family":"Piukovics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1rp\u00e1d","family":"Szomor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Gopcsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3507-9997","authenticated-orcid":false,"given":"Zs\u00f3fia","family":"Milt\u00e9nyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"4204_CR1","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1200\/JCO.2004.12.170","volume":"22","author":"G Bonadonna","year":"2004","unstructured":"Bonadonna G, Bonfante V, Viviani S, di Russo A, Villani F, Valagussa P (2004) ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin\u2019s disease: long-term results. J Clin Oncol 22:2835\u20132841. https:\/\/doi.org\/10.1200\/JCO.2004.12.170","journal-title":"J Clin Oncol"},{"key":"4204_CR2","doi-asserted-by":"publisher","first-page":"4548","DOI":"10.1200\/JCO.2008.19.8820","volume":"27","author":"A Engert","year":"2009","unstructured":"Engert A, Diehl V, Franklin J, Lohri A, D\u00f6rken B, Ludwig WD, Koch P, H\u00e4nel M, Pfreundschuh M, Wilhelm M, Tr\u00fcmper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, M\u00fcller-Hermelink HK, Hasenclever D, L\u00f6ffler M (2009) Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin\u2019s lymphoma: 10\u00a0years of follow-up of the GHSG HD9 study. J Clin Oncol 27:4548\u20134554. https:\/\/doi.org\/10.1200\/JCO.2008.19.8820","journal-title":"J Clin Oncol"},{"key":"4204_CR3","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1016\/j.bbmt.2006.06.006","volume":"12","author":"NS Majhail","year":"2006","unstructured":"Majhail NS, Weisdorf DJ, Defor TE, Miller JS, McGlave PB, Slungaard A, Arora M, Ramsay NKC, Orchard PJ, MacMillan ML, Burns LJ (2006) Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin\u2019s lymphoma. Biol Blood Marrow Transplant 12:1065\u20131072. https:\/\/doi.org\/10.1016\/j.bbmt.2006.06.006","journal-title":"Biol Blood Marrow Transplant"},{"key":"4204_CR4","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/annonc\/mdi119","volume":"16","author":"A Sureda","year":"2005","unstructured":"Sureda A, Constans M, Iriondo A, Arranz R, Caballero MD, Vidal MJ, Petit J, L\u00f3pez A, Lahuerta JJ, Carreras E, Garc\u00eda-Conde J, Garc\u00eda-Lara\u00f1a J, Cabrera R, Jarque I, Carrera D, Garc\u00eda-Ruiz JC, Pascual MJ, Rif\u00f3n J, Moraleda JM, P\u00e9rez-Equiza K, Alb\u00f3 C, D\u00edaz-Mediavilla J, Torres A, Torres P, Besalduch J, Mar\u00edn J, Mateos MV, Fern\u00e1ndez-Ra\u00f1ada JM, Sierra J, Conde E (2005) Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin\u2019s lymphoma autografted after a first relapse. Ann Oncol 16:625\u2013633. https:\/\/doi.org\/10.1093\/annonc\/mdi119","journal-title":"Ann Oncol"},{"key":"4204_CR5","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1182\/blood-2011-10-388058","volume":"119","author":"CH Moskowitz","year":"2012","unstructured":"Moskowitz CH, Matasar MJ, Zelenetz AD, Nimer SD, Gerecitano J, Hamlin P, Horwitz S, Moskowitz AJ, Noy A, Palomba L, Perales MA, Portlock C, Straus D, Maragulia JC, Schoder H, Yahalom J (2012) Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood 119:1665\u20131670. https:\/\/doi.org\/10.1182\/blood-2011-10-388058","journal-title":"Blood"},{"key":"4204_CR6","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1182\/blood.V97.3.616","volume":"97","author":"CH Moskowitz","year":"2001","unstructured":"Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O'Brien JP, Straus D, Portlock CS, Yahalom J (2001) A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood 97:616\u2013623. https:\/\/doi.org\/10.1182\/blood.V97.3.616","journal-title":"Blood"},{"key":"4204_CR7","doi-asserted-by":"publisher","first-page":"4934","DOI":"10.1182\/blood-2010-05-282756","volume":"116","author":"AJ Moskowitz","year":"2010","unstructured":"Moskowitz AJ, Yahalom J, Kewalramani T, Maragulia JC, Vanak JM, Zelenetz AD, Moskowitz CH (2010) Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood 116:4934\u20134937. https:\/\/doi.org\/10.1182\/blood-2010-05-282756","journal-title":"Blood"},{"key":"4204_CR8","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1093\/annonc\/mdf221","volume":"13","author":"A Josting","year":"2002","unstructured":"Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH, D\u00f6rken B, Hossfeld DK, Diehl V, Engert A, Participating Centers (2002) Time-intensified dexamethasone\/cisplatin\/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin\u2019s disease. Ann Oncol 13:1628\u20131635. https:\/\/doi.org\/10.1093\/annonc\/mdf221","journal-title":"Ann Oncol"},{"key":"4204_CR9","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1093\/annonc\/mdm090","volume":"18","author":"NL Bartlett","year":"2007","unstructured":"Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K, Zelenetz AD, Cheson BD, Canellos GP (2007) Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin\u2019s lymphoma: CALGB 59804. Ann Oncol 18:1071\u20131079. https:\/\/doi.org\/10.1093\/annonc\/mdm090","journal-title":"Ann Oncol"},{"key":"4204_CR10","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1470-2045(17)30913-0","volume":"19","author":"U Vitolo","year":"2018","unstructured":"Vitolo U, Chiappella A (2018) Salvage regimens for Hodgkin\u2019s lymphoma in the brentuximab vedotin era. Lancet Oncol 19:162\u2013163","journal-title":"Lancet Oncol"},{"key":"4204_CR11","doi-asserted-by":"publisher","first-page":"3293","DOI":"10.1200\/JCO.2016.66.4466","volume":"34","author":"A Santoro","year":"2016","unstructured":"Santoro A, Mazza R, Pulsoni A, Re A, Bonfichi M, Zilioli VR, Salvi F, Merli F, Anastasia A, Luminari S, Annechini G, Gotti M, Peli A, Liberati AM, di Renzo N, Castagna L, Giordano L, Carlo-Stella C (2016) Bendamustine in combination with gemcitabine and vinorelbine is an effective regimen as induction chemotherapy before autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma: final results of a multicenter phase II study. J Clin Oncol 34:3293\u20133299. https:\/\/doi.org\/10.1200\/JCO.2016.66.4466","journal-title":"J Clin Oncol"},{"key":"4204_CR12","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1200\/JCO.2011.38.0410","volume":"30","author":"A Younes","year":"2012","unstructured":"Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin\u2019s lymphoma. J Clin Oncol 30:2183\u20132189. https:\/\/doi.org\/10.1200\/JCO.2011.38.0410","journal-title":"J Clin Oncol"},{"key":"4204_CR13","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1182\/blood-2016-02-699850","volume":"128","author":"R Chen","year":"2016","unstructured":"Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, Fong A, Younes A (2016) Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 128:1562\u20131566. https:\/\/doi.org\/10.1182\/blood-2016-02-699850","journal-title":"Blood"},{"key":"4204_CR14","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1182\/blood-2014-08-595801","volume":"125","author":"AK Gopal","year":"2015","unstructured":"Gopal AK, Chen R, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Chi X, Sievers EL, Younes A (2015) Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood 125:1236\u20131243. https:\/\/doi.org\/10.1182\/blood-2014-08-595801","journal-title":"Blood"},{"key":"4204_CR15","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1200\/JCO.2012.45.3308","volume":"31","author":"AJ Moskowitz","year":"2013","unstructured":"Moskowitz AJ, Hamlin PA, Perales MA et al (2013) Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 31:456\u2013460. https:\/\/doi.org\/10.1200\/JCO.2012.45.3308","journal-title":"J Clin Oncol"},{"key":"4204_CR16","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1182\/blood-2017-11-815183","volume":"132","author":"AS LaCasce","year":"2018","unstructured":"LaCasce AS, Gregory Bociek R, Sawas A et al (2018) Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood 132:40\u201348. https:\/\/doi.org\/10.1182\/blood-2017-11-815183","journal-title":"Blood"},{"key":"4204_CR17","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S1470-2045(17)30912-9","volume":"19","author":"OA O\u2019Connor","year":"2018","unstructured":"O\u2019Connor OA, Lue JK, Sawas A et al (2018) Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin\u2019s lymphoma: an international, multicentre, single-arm, phase 1\u20132 trial. Lancet Oncol 19:257\u2013266. https:\/\/doi.org\/10.1016\/S1470-2045(17)30912-9","journal-title":"Lancet Oncol"},{"key":"4204_CR18","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41408-019-0265-x","volume":"9","author":"A Broccoli","year":"2019","unstructured":"Broccoli A, Argnani L, Botto B et al (2019) First salvage treatment with bendamustine and brentuximab vedotin in Hodgkin lymphoma: a phase 2 study of the Fondazione Italiana Linfomi. Blood Cancer J 9:100. https:\/\/doi.org\/10.1038\/s41408-019-0265-x","journal-title":"Blood Cancer J"},{"key":"4204_CR19","unstructured":"European Medicines Agency (2020) Adcetris. European Medicines Agency website. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/adcetris. Accessed 26 Jan 2020"},{"key":"4204_CR20","first-page":"185","volume":"3","author":"\u00c1 Ill\u00e9s","year":"2016","unstructured":"Ill\u00e9s \u00c1, Moln\u00e1r Z, Milt\u00e9nyi Z (2016) Novelties in the management of Hodgkin lymphoma. Klin Onkol 3:185\u2013193","journal-title":"Klin Onkol"},{"key":"4204_CR21","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1182\/blood-2016-05-718528","volume":"128","author":"BD Cheson","year":"2016","unstructured":"Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, Hoos A, Barrington SF, Armand P (2016) Refinement of the Lugano classification lymphoma response criteria in the era of immunomodulatory therapy. Blood 128:2489\u20132496. https:\/\/doi.org\/10.1182\/blood-2016-05-718528","journal-title":"Blood"},{"key":"4204_CR22","unstructured":"Seattle Genetics Inc. (2020) ADCETRIS\u00ae (brentuximab vedotin) [package insert]. U.S. Food and Drug Administration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/125388_S056S078lbl.pdf. Accessed 26 Jan 2020"},{"key":"4204_CR23","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/cncr.24714","volume":"116","author":"BS Kahl","year":"2010","unstructured":"Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD (2010) Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer 116:106\u2013114. https:\/\/doi.org\/10.1002\/cncr.24714","journal-title":"Cancer"},{"key":"4204_CR24","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/01.hs9.0000547978.61156.2d","volume":"2","author":"D Martineau","year":"2018","unstructured":"Martineau D, Sauvezie M, Oberic L et al (2018) Brentuximab-vedotin + bendamustine: a highly effective salvage treatment in refractory\/relapsed patients with Hodgkin lymphoma. HemaSphere 2:53. https:\/\/doi.org\/10.1097\/01.hs9.0000547978.61156.2d","journal-title":"HemaSphere"},{"key":"4204_CR25","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1182\/blood-2018-07-861641","volume":"132","author":"CH Moskowitz","year":"2018","unstructured":"Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Viviani S, Bachanova V, Sureda A, McClendon T, Lee C, Lisano J, Sweetenham J (2018) Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood 132:2639\u20132642. https:\/\/doi.org\/10.1182\/blood-2018-07-861641","journal-title":"Blood"},{"key":"4204_CR26","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1182\/blood-2017-10-811224","volume":"131","author":"AF Herrera","year":"2018","unstructured":"Herrera AF, Moskowitz AJ, Bartlett NL, Vose JM, Ramchandren R, Feldman TA, LaCasce AS, Ansell SM, Moskowitz CH, Fenton K, Ogden CA, Taft D, Zhang Q, Kato K, Campbell M, Advani RH (2018) Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood 131:1183\u20131194. https:\/\/doi.org\/10.1182\/blood-2017-10-811224","journal-title":"Blood"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-020-04204-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-020-04204-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-020-04204-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T23:27:32Z","timestamp":1627946852000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-020-04204-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,3]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["4204"],"URL":"https:\/\/doi.org\/10.1007\/s00277-020-04204-1","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,3]]},"assertion":[{"value":"27 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Approval was obtained from the ethics committees of all participating centers. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}