{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:44:58Z","timestamp":1772811898717,"version":"3.50.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:00:00Z","timestamp":1545177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:00:00Z","timestamp":1545177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1038\/s41375-018-0313-8","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T14:41:46Z","timestamp":1545230506000},"page":"1161-1172","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia"],"prefix":"10.1038","volume":"33","author":[{"given":"Julia","family":"von Tresckow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Cramer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Bahlo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Robrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Langerbeins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Maria","family":"Fink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-0570","authenticated-orcid":false,"given":"Othman","family":"Al-Sawaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Illmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Klaproth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Estenfelder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Ritgen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens-Martin","family":"Wendtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl-Anton","family":"Kreuzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Stilgenbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"B\u00f6ttcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara F.","family":"Eichhorst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"key":"313_CR1","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1182\/blood.V126.23.4151.4151","volume":"126","author":"J von Tresckow","year":"2015","unstructured":"von Tresckow J, Cramer P, Bahlo J, Engelke A, Langerbeins P, Fink A-M, et al. CLL2-BIG\u2014a novel treatment regimen of bendamustine followed by GA101 and ibrutinib followed by ibrutinib and GA101 maintenance in patients with chronic lymphocytic leukemia (CLL): interim results of a phase II-trial. Blood. 2015;126:4151.","journal-title":"Blood"},{"key":"313_CR2","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1182\/blood.V128.22.640.640","volume":"128","author":"J von Tresckow","year":"2016","unstructured":"von Tresckow J, Cramer P, Bahlo J, Robrecht S, Engelke A, Langerbeins P, et al. CLL2-BIG\u2014a novel treatment regimen of bendamustine followed by GA101 and ibrutinib followed by ibrutinib and GA101 maintenance in patients with chronic lymphocytic leukemia (CLL): results of a phase II-trial. Blood. 2016;128:640.","journal-title":"Blood"},{"key":"313_CR3","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1200\/JCO.2013.49.6547","volume":"32","author":"P Hillmen","year":"2014","unstructured":"Hillmen P, Gribben JG, Follows GA, Milligan D, Sayala HA, Moreton P, et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study. J Clin Oncol. 2014;32:1236\u201341.","journal-title":"J Clin Oncol"},{"key":"313_CR4","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1056\/NEJMoa1313984","volume":"370","author":"V Goede","year":"2014","unstructured":"Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370:1101\u201310.","journal-title":"N Engl J Med"},{"key":"313_CR5","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1002\/ajh.23668","volume":"89","author":"R Foa","year":"2014","unstructured":"Foa R, Del Giudice I, Cuneo A, Del Poeta G, Ciolli S, Di Raimondo F, et al. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients. Am J Hematol. 2014;89:480\u20136.","journal-title":"Am J Hematol"},{"issue":"7","key":"313_CR6","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1016\/S1470-2045(16)30051-1","volume":"17","author":"Barbara Eichhorst","year":"2016","unstructured":"Eichhorst B, Fink A-M, Bahlo J, Busch R, Kovacs G, Maurer C, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17:928\u201342.","journal-title":"The Lancet Oncology"},{"key":"313_CR7","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1182\/blood-2015-06-651125","volume":"127","author":"K Fischer","year":"2016","unstructured":"Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127:208\u201315.","journal-title":"Blood"},{"key":"313_CR8","doi-asserted-by":"publisher","first-page":"499","DOI":"10.2217\/fon-2017-0442","volume":"14","author":"P Cramer","year":"2018","unstructured":"Cramer P, von Tresckow J, Bahlo J, Engelke A, Langerbeins P, Fink AM, et al. CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia. Future Oncol. 2018;14:499\u2013513.","journal-title":"Future Oncol"},{"key":"313_CR9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1056\/NEJMoa1215637","volume":"369","author":"JC Byrd","year":"2013","unstructured":"Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32\u201342.","journal-title":"N Engl J Med"},{"key":"313_CR10","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/S1470-2045(14)70335-3","volume":"15","author":"JA Burger","year":"2014","unstructured":"Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, Rosin NY, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014;15:1090\u20139.","journal-title":"Lancet Oncol"},{"key":"313_CR11","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.1182\/blood.V126.23.4157.4157","volume":"126","author":"L Ysebaert","year":"2015","unstructured":"Ysebaert L, Klein C, Quillet-Mary A. CLL cells from ibrutinib-induced lymphocytosis of relapsed\/refractory chronic lymphocytic leukemia patients are responsive to obinutuzumab, but not rituximab, ex vivo. Blood. 2015;126:4157.","journal-title":"Blood"},{"issue":"23","key":"313_CR12","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1182\/blood-2013-05-498287","volume":"122","author":"M. Hallek","year":"2013","unstructured":"Hallek M. Signaling the end of chronic lymphocytic leukemia?: new frontline treatment strategies. Blood. 2013;122:3723\u201334.","journal-title":"Blood"},{"key":"313_CR13","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1182\/blood-2007-06-093906","volume":"111","author":"M Hallek","year":"2008","unstructured":"Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446\u201356.","journal-title":"Blood"},{"key":"313_CR14","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1200\/JCO.2011.36.9348","volume":"30","author":"S B\u00f6ttcher","year":"2012","unstructured":"B\u00f6ttcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012;30:980\u20138.","journal-title":"J Clin Oncol"},{"key":"313_CR15","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.1200\/JCO.2010.33.8061","volume":"29","author":"K Fischer","year":"2011","unstructured":"Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, Schweighofer CD, et al. Bendamustine combined with rituximab in patients with relapsed and\/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011;29:3559\u201366.","journal-title":"J Clin Oncol"},{"key":"313_CR16","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1200\/JCO.2011.39.2688","volume":"30","author":"K Fischer","year":"2012","unstructured":"Fischer K, Cramer P, Busch R, Bottcher S, Bahlo J, Schubert J, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2012;30:3209\u201316.","journal-title":"J Clin Oncol"},{"key":"313_CR17","first-page":"1357","volume":"90","author":"M Bergmann","year":"2005","unstructured":"Bergmann M, Goebeler M, Herold M, Emmerich B, Wilhelm M, Ruelfs C, et al. Efficacy of bendamustine in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase I\/II study of the German CLL Study Group. Haematologica. 2005;90:1357\u201364.","journal-title":"Haematologica"},{"key":"313_CR18","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/bjh.12000","volume":"159","author":"WU Knauf","year":"2012","unstructured":"Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012;159:67\u201377.","journal-title":"Br J Haematol"},{"key":"313_CR19","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","volume":"373","author":"JA Burger","year":"2015","unstructured":"Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. New Engl J Med. 2015;373:2425\u201337.","journal-title":"New Engl J Med"},{"key":"313_CR20","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1200\/JCO.2016.67.1305","volume":"34","author":"G Kovacs","year":"2016","unstructured":"Kovacs G, Robrecht S, Fink AM, Bahlo J, Cramer P, Tresckow Jv, et al. Minimal residual disease assessment improves prediction of outcome in patients with chronic lymphocytic leukemia (CLL) who achieve partial response: comprehensive analysis of two phase III studies of the German CLL Study Group. J Clin Oncol. 2016;34:3758\u201365.","journal-title":"J Clin Oncol"},{"key":"313_CR21","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1182\/blood-2014-10-606038","volume":"125","author":"JC Byrd","year":"2015","unstructured":"Byrd JC, Furman RR, Coutre SE, Burger JA, Blum KA, Coleman M, et al. Three-year follow-up of treatment-na\u00efve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015;125:2497\u2013506.","journal-title":"Blood"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-018-0313-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-018-0313-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-018-0313-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T06:13:13Z","timestamp":1659075193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-018-0313-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,19]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["313"],"URL":"https:\/\/doi.org\/10.1038\/s41375-018-0313-8","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,19]]},"assertion":[{"value":"7 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2018","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":"JvT: Research funding (F. Hoffmann-LaRoche, Janssen-Cilag), honoraria and consultant or advisory board member (AbbVie, Janssen-Cilag and F. Hoffmann-LaRoche), travel grants (AbbVie, Celgene, F. Hoffmann-LaRoche and Janssen-Cilag). PC: Research funding (AbbVie, Gilead, GlaxoSmithKline\/Novartis, F. Hoffmann-LaRoche, and Janssen-Cilag), honoraria (F. Hoffmann-LaRoche and Janssen-Cilag), consultant or advisory board member (AbbVie, AstraZeneca, Janssen-Cilag and Novartis) and travel grants (Astellas, F. Hoffmann LaRoche, Gilead, Janssen-Cilag and Mundipharma). JB: Honoraria and travel grants (F. Hoffmann-LaRoche). PL: Research funding (Janssen-Cilag), Honoraria (AbbVie, Janssen-Cilag and F. Hoffmann-LaRoche), travel grants (AbbVie, F. Hoffmann-LaRoche, Janssen-Cilag and Mundipharma) AF: Research funding (Celgene), honoraria (F. Hoffman-LaRoche) and travel grants (F. Hoffmann-LaRoche, Mundipharma, Abbvie and Celgene). OA: Honoraria and consultant or advisory board member (AbbVie, Gilead and F. Hoffmann-LaRoche), travel grants (AbbVie, Gilead, F. Hoffmann-LaRoche and Janssen-Cilag). TI: Travel grants (F. Hoffmann-LaRoche). MR: Research funding (AbbVie; F. Hoffmann-LaRoche), consultant or advisory board member (AbbVie, BMS, F. Hoffmann-LaRoche) and travel grants (F. Hoffmann-LaRoche). KF: Travels grants (F. Hoffmann-LaRoche). CMW: Honoraria, consultant or advisory board member, research funding and travel grants (AbbVie, Gilead, F. Hoffmann-LaRoche, Janssen-Cilag and Mundipharma). KK: Research funding, honoraria, consultant or advisory board member and speaker\u00b4s bureau (F. Hoffmann-LaRoche, Janssen-Cilag and Mundipharma). SS: Research support, honoraria, consultant or advisory board member, speaker\u00b4s bureau and travel support (AbbVie, Amgen, Astra-Zeneca, Celgene, F. Hoffmann-LaRoche, Gilead, GlaxoSmithKline, Janssen-Cilag and Novartis). SB: Reasearch funding (AbbVie, Celgene and F. Hoffmann-LaRoche), honoraria (AbbVie, Becton Dickinson, F. Hoffmann-LaRoche), consultant or advisory board member (F. Hoffmann-LaRoche), travel grants (Celgene, F. Hoffmann-LaRoche). BE: Research support, consultant or advisory board member and travel support (AbbVie, Celgene, F. Hoffmann-LaRoche, Gilead, GlaxoSmithKline, Janssen-Cilag, Mundipharma). MH: Research funding (AbbVie, Celgene, F. Hoffmann-LaRoche, Gilead, Janssen-Cilag, Mundipharma and Pharmacyclics), honoraria and speaker\u00b4s bureau (AbbVie, Boehringer-Ingelheim, Celgene, F. Hoffmann-LaRoche, Gilead, Janssen-Cilag, Mundipharma and Pharmacyclics) and consultant or advisory board member (AbbVie, F. Hoffmann-LaRoche, Gilead, Janssen-Cilag). The remaining authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}