{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:02:54Z","timestamp":1740106974354,"version":"3.37.3"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinik M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma and commonly used induction immunochemotherapies include the anti-CD20 antibody rituximab. However, efficacy data for rituximab regarding overall survival (OS) in first line MCL therapy remain conflicting.<\/jats:p><jats:p>We report long-term outcomes of a pooled trials analysis comparing Cyclophosphamide, Doxorubicine, Vincristine, Prednisone (CHOP) to R-CHOP in MCL to confirm efficacy on failure free survival (FFS) and OS in relevant subgroups. Untreated, adult MCL patients of two prospective trials assigned to CHOP or R-CHOP were included. Primary endpoints were FFS and OS, secondary endpoints included duration of response (DOR), secondary malignancies and OS after relapse. Between 1996 and 2003, 385 MCL patients were assigned to CHOP (201) or R-CHOP (184). After a median follow-up of 13.4 years, the addition of Rituximab significantly improved FFS (1.36 vs. 2.07 years, HR 0.62 (0.50\u20130.77)), OS (4.84 vs. 5.81 years, HR 0.78 (0.61\u20130.99)) and DOR (1.48 vs. 2.08 years, HR 0.67 (0.53\u20130.86)). Furthermore, Rituximab improved survival across different MCL risk groups. In a post-hoc analysis of OS after relapse comparing patients receiving chemotherapy with \/ without rituximab, rituximab maintained efficacy with a median OS of 3.10 vs. 2.11 years (HR 0.70, 0.54\u20130.91). The rate of secondary malignancies was 0.5 and 3.9% for hematological and 7 and 8% for non-hematological malignancies for CHOP and R-CHOP patients, respectively. We present mature results of a pooled MCL cohort, demonstrating prolonged FFS, OS and DOR for the combined immuno-chemotherapy, confirming the standard of care in first line treatment.<\/jats:p>","DOI":"10.1007\/s00277-023-05385-1","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T08:01:56Z","timestamp":1691481716000},"page":"2791-2801","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma\u2014a pooled trials analysis"],"prefix":"10.1007","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2444-416X","authenticated-orcid":false,"given":"Luca","family":"Fischer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linmiao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg Thomas","family":"Bittenbring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Huebel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Duell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Metzner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juergen","family":"Krauter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertram","family":"Glass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Huettmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Schaefer-Eckart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Silkenstedt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Hiddemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Unterhalt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Dreyling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Hoster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the German Lymphoma Alliance (GLA) and the German Low-Grade Lymphoma Study Group (GLSG)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"issue":"9","key":"5385_CR1","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1038\/bjc.2015.94","volume":"112","author":"A Smith","year":"2015","unstructured":"Smith A, Crouch S, Lax S et al (2015) Lymphoma incidence, survival and prevalence 2004\u20132014: sub-type analyses from the UK\u2019s Haematological malignancy research network. Br J Cancer 112(9):1575\u20131584","journal-title":"Br J Cancer"},{"issue":"18","key":"5385_CR2","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1200\/JCO.2016.71.2083","volume":"35","author":"C Laurent","year":"2017","unstructured":"Laurent C, Baron M, Amara N et al (2017) Impact of expert pathologic review of lymphoma diagnosis: study of patients from the french Lymphopath network. J Clin Oncol 35(18):2008\u20132017","journal-title":"J Clin Oncol"},{"issue":"19","key":"5385_CR3","doi-asserted-by":"publisher","first-page":"3724","DOI":"10.1182\/blood-2010-05-282632","volume":"116","author":"M Sant","year":"2010","unstructured":"Sant M, Allemani C, Tereanu C et al (2010) Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 116(19):3724\u20133734","journal-title":"Blood"},{"issue":"suppl_4","key":"5385_CR4","doi-asserted-by":"publisher","first-page":"iv62","DOI":"10.1093\/annonc\/mdx223","volume":"28","author":"M Dreyling","year":"2017","unstructured":"Dreyling M, Campo E, Hermine O et al (2017) Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28(suppl_4):iv62\u2013iv71","journal-title":"Ann Oncol"},{"issue":"2","key":"5385_CR5","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1182\/blood-2007-06-095331","volume":"111","author":"E Hoster","year":"2008","unstructured":"Hoster E, Dreyling M, Klapper W et al (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111(2):558\u2013565","journal-title":"Blood"},{"issue":"13","key":"5385_CR6","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1200\/JCO.2013.52.2466","volume":"32","author":"E Hoster","year":"2014","unstructured":"Hoster E, Klapper W, Hermine O et al (2014) Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol 32(13):1338\u20131346","journal-title":"J Clin Oncol"},{"issue":"12","key":"5385_CR7","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1200\/JCO.2015.63.8387","volume":"34","author":"E Hoster","year":"2016","unstructured":"Hoster E, Rosenwald A, Berger F et al (2016) Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: results from randomized trials of the European mantle cell lymphoma network. J Clin Oncol 34(12):1386\u20131394","journal-title":"J Clin Oncol"},{"issue":"10044","key":"5385_CR8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0140-6736(16)00739-X","volume":"388","author":"O Hermine","year":"2016","unstructured":"Hermine O, Hoster E, Walewski J et al (2016) Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet 388(10044):565\u2013575","journal-title":"Lancet"},{"issue":"3","key":"5385_CR9","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1111\/bjh.14241","volume":"175","author":"CW Eskelund","year":"2016","unstructured":"Eskelund CW, Kolstad A, Jerkeman M et al (2016) 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol 175(3):410\u2013418","journal-title":"Br J Haematol"},{"issue":"1","key":"5385_CR10","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1182\/blood-2011-09-370320","volume":"121","author":"R Delarue","year":"2013","unstructured":"Delarue R, Haioun C, Ribrag V et al (2013) CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d\u2019Etude des Lymphomes de l\u2019Adulte. Blood 121(1):48\u201353","journal-title":"Blood"},{"issue":"16","key":"5385_CR11","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1182\/blood-2018-03-791392","volume":"132","author":"K Maddocks","year":"2018","unstructured":"Maddocks K (2018) Update on mantle cell lymphoma. Blood 132(16):1647\u20131656","journal-title":"Blood"},{"issue":"5","key":"5385_CR12","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1002\/cncr.22093","volume":"107","author":"C Nickenig","year":"2006","unstructured":"Nickenig C, Dreyling M, Hoster E et al (2006) Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low\u2010Grade Lymphoma Study Group. Cancer: Interdiscip Int J Am Cancer Soc 107(5):1014\u20131022","journal-title":"Cancer: Interdiscip Int J Am Cancer Soc"},{"issue":"9","key":"5385_CR13","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1200\/JCO.2005.08.133","volume":"23","author":"G Lenz","year":"2005","unstructured":"Lenz G, Dreyling M, Hoster E et al (2005) Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 23(9):1984\u20131992","journal-title":"J Clin Oncol"},{"issue":"7","key":"5385_CR14","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1182\/blood-2004-10-3883","volume":"105","author":"M Dreyling","year":"2005","unstructured":"Dreyling M, Lenz G, Hoster E et al (2005) Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood 105(7):2677\u20132684","journal-title":"Blood"},{"issue":"10","key":"5385_CR15","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1182\/blood-2004-04-1323","volume":"104","author":"R Forstpointner","year":"2004","unstructured":"Forstpointner R, Dreyling M, Repp R et al (2004) The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 104(10):3064\u20133071","journal-title":"Blood"},{"issue":"11","key":"5385_CR16","doi-asserted-by":"publisher","first-page":"4474","DOI":"10.1182\/blood.V110.11.4474.4474","volume":"110","author":"M Herold","year":"2007","unstructured":"Herold M, Haas A, Srock S et al (2007) Immunochemotherapy (R-MCP) Is Not Superior to Chemotherapy (MCP) Alone in Advanced Mantle Cell Lymphoma - 42 Months Follow Up Results of the OSHO 39 Study. Blood 110(11):4474\u20134474","journal-title":"Blood"},{"issue":"2","key":"5385_CR17","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3324\/haematol.2015.128710","volume":"101","author":"S Rule","year":"2016","unstructured":"Rule S, Smith P, Johnson PW et al (2016) The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. Haematologica 101(2):235\u2013240","journal-title":"Haematologica"},{"key":"5385_CR18","first-page":"Cd003805","volume":"4","author":"H Schulz","year":"2007","unstructured":"Schulz H, Bohlius J, Skoetz N et al (2007) Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin\u2019s lymphoma. Cochrane Database Syst Rev 4:Cd003805","journal-title":"Cochrane Database Syst Rev"},{"issue":"9","key":"5385_CR19","doi-asserted-by":"publisher","first-page":"e648","DOI":"10.1016\/S2352-3026(21)00195-2","volume":"8","author":"AK Zoellner","year":"2021","unstructured":"Zoellner AK, Unterhalt M, Stilgenbauer S et al (2021) Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol 8(9):e648\u2013e657","journal-title":"Lancet Haematol"},{"issue":"4","key":"5385_CR20","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1200\/JCO.1999.17.4.1244","volume":"17","author":"BD Cheson","year":"1999","unstructured":"Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin\u2019s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244","journal-title":"J Clin Oncol"},{"issue":"6","key":"5385_CR21","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1038\/leu.2015.322","volume":"30","author":"E Hoster","year":"2016","unstructured":"Hoster E, Geisler CH, Doorduijn J et al (2016) Total body irradiation after high-dose cytarabine in mantle cell lymphoma: a comparison of Nordic MCL2, HOVON-45, and European MCL Younger trials. Leukemia 30(6):1428\u20131430","journal-title":"Leukemia"},{"issue":"22","key":"5385_CR22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1182\/blood.V128.22.145.145","volume":"128","author":"S Le Gouill","year":"2016","unstructured":"Le Gouill S, Thieblemont C, Oberic L et al (2016) Rituximab maintenance after autologous stem cell transplantation prolongs survival in younger patients with mantle cell lymphoma: final results of the randomized phase 3 Lyma trial of the Lysa\/Goelams Group. Blood 128(22):145\u2013145","journal-title":"Blood"},{"issue":"6","key":"5385_CR23","doi-asserted-by":"publisher","first-page":"949","DOI":"10.3324\/haematol.12656","volume":"93","author":"N Inga","year":"2008","unstructured":"Inga N, Jos\u00e9 IM-S, Florian W et al (2008) Recurrent loss of the Y chromosome and homozygous deletions within the pseudoautosomal region 1: association with male predominance in mantle cell lymphoma. Haematologica 93(6):949\u2013950","journal-title":"Haematologica"},{"issue":"14","key":"5385_CR24","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1182\/blood-2011-09-380949","volume":"119","author":"C M\u00fcller","year":"2012","unstructured":"M\u00fcller C, Murawski N, Wiesen MH et al (2012) The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood 119(14):3276\u20133284","journal-title":"Blood"},{"issue":"5","key":"5385_CR25","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1182\/blood-2013-07-517037","volume":"123","author":"M Pfreundschuh","year":"2014","unstructured":"Pfreundschuh M, M\u00fcller C, Zeynalova S et al (2014) Suboptimal dosing of rituximab in male and female patients with DLBCL. Blood 123(5):640\u2013646","journal-title":"Blood"},{"issue":"8","key":"5385_CR26","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1111\/bcp.13271","volume":"83","author":"S Rozman","year":"2017","unstructured":"Rozman S, Grabnar I, Novakovi\u0107 S et al (2017) Population pharmacokinetics of rituximab in patients with diffuse large B-cell lymphoma and association with clinical outcome. Br J Clin Pharmacol 83(8):1782\u20131790","journal-title":"Br J Clin Pharmacol"},{"issue":"5","key":"5385_CR27","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/bjh.14114","volume":"174","author":"Y Sawalha","year":"2016","unstructured":"Sawalha Y, Rouphail B, Jia X et al (2016) Is rituximab sub-optimally dosed in indolent B cell lymphoma? Br J Haematol 174(5):721\u2013729","journal-title":"Br J Haematol"},{"issue":"9","key":"5385_CR28","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.3324\/haematol.2011.059246","volume":"97","author":"U J\u00e4ger","year":"2012","unstructured":"J\u00e4ger U, Fridrik M, Zeitlinger M et al (2012) Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Haematologica 97(9):1431\u20131438","journal-title":"Haematologica"},{"issue":"22","key":"5385_CR29","doi-asserted-by":"publisher","first-page":"3706","DOI":"10.1182\/blood.V114.22.3706.3706","volume":"114","author":"C Buske","year":"2009","unstructured":"Buske C, Hoster E, Dreyling MH et al (2009) Rituximab overcomes sex as a strong adverse prognostic factor for treatment outcome in patients with follicular lymphoma: analysis of patients treated with rituximab\/chop or chop in randomized trials of the German low grade lymphoma study group (GLSG). Blood 114(22):3706\u20133706","journal-title":"Blood"},{"issue":"4","key":"5385_CR30","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/s41375-019-0630-6","volume":"34","author":"M F\u00fcrstenau","year":"2020","unstructured":"F\u00fcrstenau M, Hopfinger G, Robrecht S et al (2020) Influence of obesity and gender on treatment outcomes in patients with chronic lymphocytic leukemia (CLL) undergoing rituximab-based chemoimmunotherapy. Leukemia 34(4):1177\u20131181","journal-title":"Leukemia"},{"issue":"5","key":"5385_CR31","doi-asserted-by":"publisher","first-page":"e211","DOI":"10.3324\/haematol.2018.205229","volume":"104","author":"S Rule","year":"2019","unstructured":"Rule S, Dreyling M, Goy A et al (2019) Ibrutinib for the treatment of relapsed\/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis. Haematologica 104(5):e211\u2013e214","journal-title":"Haematologica"},{"key":"5385_CR32","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s41375-020-01013-3","volume":"35","author":"C Visco","year":"2020","unstructured":"Visco C, Di Rocco A, Evangelista A et al (2020) Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study. Leukemia 35:787","journal-title":"Leukemia"},{"issue":"2","key":"5385_CR33","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/bjh.17363","volume":"193","author":"R McCulloch","year":"2021","unstructured":"McCulloch R, Lewis D, Crosbie N et al (2021) Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients. Br J Haematol 193(2):290\u2013298","journal-title":"Br J Haematol"},{"issue":"1","key":"5385_CR34","doi-asserted-by":"publisher","first-page":"e510","DOI":"10.1097\/HS9.0000000000000510","volume":"5","author":"CW Eskelund","year":"2021","unstructured":"Eskelund CW, Dimopoulos K, Kolstad A et al (2021) Detailed long-term follow-up of patients who relapsed after the Nordic mantle cell lymphoma trials: MCL2 and MCL3. Hemasphere 5(1):e510","journal-title":"Hemasphere"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-023-05385-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-023-05385-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-023-05385-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T10:05:40Z","timestamp":1694253940000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-023-05385-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["5385"],"URL":"https:\/\/doi.org\/10.1007\/s00277-023-05385-1","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"type":"print","value":"0939-5555"},{"type":"electronic","value":"1432-0584"}],"subject":[],"published":{"date-parts":[[2023,8,8]]},"assertion":[{"value":"8 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients provided written informed consent. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Both trials were performed in accordance with local regulations and approved by the responsible ethics committees (Ethikkommission der Medizinischen Fakult\u00e4t G\u00f6ttingen (GLSG1996); Ethikkommission der Medizinischen Fakult\u00e4t der LMU (GLSG2000). The trials were started before preregistration was implemented and are therefore not registered.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Bittenbring JT received travel support and honoraria from Gilead, Incyte and MDS.H\u00fcbel K served as an advisor and consultant for Roche, Celgene\/BMS, Gilead, Incyte, EUSA, Novartis, received honoraria from Roche, Celgene\/BMS, Servier, EUSA, BeiGene, Novartis and research support from Roche, Alexion, Celgene\/BMS, Janssen, Incyte.Schmidt C served as a consultant for Novartis, Kite\/Gilead, Takeda, BMS, received honoraria from Novartis, Kite\/Gilead, travel support from Novartis, Kite\/Gilead, Takeda, BMS, Janssen and research funding from Kite\/Gilead.Gla\u00df B served as a consultant for BMS, Roche, Riemser, Kite, Novartis, served in the speakers bureau of Roche and received research funding from Roche and Riemser.H\u00fcttmann A received honoraria from Celgene, Gilead, Takeda, served as a consultant for Lead Discovery Center GmbH and is a member of a Board or Advisory Committee for Takeda.Hiddemann W received research support from Roche.Unterhalt M received research support from Roche.Dreyling M received speaker\u2019s honoraria from Amgen, Astra Zeneca, Bayer, BMS\/Celgene, Gilead\/Kite, Incyte, Janssen, Novartis, Roche, served on scientific advisory bords for Astra Zeneca, Bayer, Beigene, BMS\/Celgene, Genmab, Gilead\/Kite, Incyte, Janssen, Lilly\/Loxo, Morphosys, Novartis, Roche and received research support from Abbvie, Bayer, BMS\/Celgene, Gilead\/Kite, Janssen, Roche.All remaining authors have declared no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}