{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:36:30Z","timestamp":1791329790293,"version":"4.3.1"},"reference-count":91,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T00:00:00Z","timestamp":1446768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007013","name":"F. Hoffman-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The management of patients with <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> is undergoing significant changes; during the last decade, the outcome of first\u2010line therapies has been markedly improved with the addition of anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>20 antibodies to chemotherapy. Today, chemoimmunotherapy for physically fit patients \u226465 years should consist of fludarabine, cyclophosphamide, and rituximab (<jats:styled-content style=\"fixed-case\">FCR<\/jats:styled-content>). The combination of bendamustine and rituximab (<jats:styled-content style=\"fixed-case\">BR<\/jats:styled-content>) should be considered in physically fit patients &gt;65 years and in patients with a higher risk of infections. Patients with reduced fitness and\/or relevant comorbidity should receive chlorambucil with a <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>20 antibody, preferably obinutuzumab. Regardless of their fitness, patients with <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> carrying genetic aberrations such as del(17p) and\/or TP53 mutation poorly respond to chemoimmunotherapy and therefore require different therapeutic approaches. An increasing understanding of the disease biology has led to the development of targeted drugs for the treatment of <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>, such as the <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> inhibitor ibrutinib and PI3K inhibitor idelalisib. These agents have shown efficacy in high\u2010risk and relapsed\/refractory patients and are currently being evaluated in clinical trials for first\u2010line therapy. It is anticipated that these compounds and further other novel agents will profoundly change the therapy of <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/ejh.12678","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T20:26:53Z","timestamp":1441225613000},"page":"9-18","source":"Crossref","is-referenced-by-count":28,"title":["Advances in first\u2010line treatment of chronic lymphocytic leukemia: current recommendations on management and first\u2010line treatment by the German <scp>CLL<\/scp> Study Group (<scp>GCLLSG<\/scp>)"],"prefix":"10.1111","volume":"96","author":[{"given":"Paula","family":"Cramer","sequence":"first","affiliation":[{"name":"Department I of Internal Medicine Center of Integrated Oncology Cologne\u2010Bonn and German CLL Study Group University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Langerbeins","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine Center of Integrated Oncology Cologne\u2010Bonn and German CLL Study Group University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Eichhorst","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine Center of Integrated Oncology Cologne\u2010Bonn and German CLL Study Group University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine Center of Integrated Oncology Cologne\u2010Bonn and German CLL Study Group University of Cologne Cologne Germany"},{"name":"CECAD \u2010 Cologne Cluster of Excellence in Cellular Stress Responses in Aging\u2010associated Diseases University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2508"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01114.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.57.1.43"},{"key":"e_1_2_8_5_1","volume-title":"Surveillance, Epidemiology, and End Results (SEER) Program: SEER Stat Database, Nov. 2008 Sub (2000\u20102006)","year":"2009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190600555819"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.2.448"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa075290"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO;2-V"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V46.2.219.219"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2010.167"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-556399"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-051458"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","unstructured":"KutschN BahloJ ByrdJC et al.The international Prognostic Index for patients with CLL (CLL\u2010IPI): An international meta\u2010analysis. ASCO 2015 Meeting Abstracts (J Clin Oncol 33; abstr 7002) 2015.","DOI":"10.1200\/jco.2015.33.15_suppl.7002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012283432602"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-09-3236"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-234708"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.24.7245"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870030104"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.10720"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-154070"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.5-3-224"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/107327480100802S01","article-title":"The geriatric cancer patient: equal benefit from equal treatment","volume":"8","author":"Balducci L","year":"2001","journal-title":"Cancer Control"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/107327480701400102"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190802688517"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.2165\/11587650-000000000-00000"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-234146"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1968.tb02103.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2395"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61125-8"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.08.0762"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61381-5"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.4556"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-140582"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.12.051"},{"key":"e_1_2_8_37_1","doi-asserted-by":"crossref","unstructured":"FischerK BahloJ FinkA\u2010M et al.Extended Follow up of the CLL8 Protocol a Randomized Phase\u2010III Trial of the German CLL Study Group (GCLLSG) Comparing Fludarabine and Cyclophosphamide (FC) to FC Plus Rituximab (FCR) for Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL): Results On Survival Progression\u2010Free Survival Delayed Neutropenias and Secondary Malignancies Confirm Superiority of the FCR Regimen. ASH Annual Meeting Abstracts 2012;120.","DOI":"10.1182\/blood.V120.21.435.435"},{"key":"e_1_2_8_38_1","doi-asserted-by":"crossref","unstructured":"FischerK BahloJ FinkA\u2010M et al.Extended follow\u2010up of the CLL8 protocol a randomized phase\u2010III trial of the german CLL study group (GCLLSG) comparing Fludarabine and Cyclophosphamide (FC) to FC plus Rituximab (FCR) for previously untreated patients with Chronic Lymphocytic Leukemia (CLL). XV iwCLL Meeting Abstracts 2013 2013.","DOI":"10.1182\/blood.V120.21.435.435"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-583765"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2007.00889.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-033274"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-011-9737-y"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25028"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.8061"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.2688"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","unstructured":"EichhorstB FinkA\u2010M BuschR et al.Frontline Chemoimmunotherapy with Fludarabine (F) Cyclophosphamide (C) and Rituximab (R) (FCR) Shows Superior Efficacy in Comparison to Bendamustine (B) and Rituximab (BR) in Previously Untreated and Physically Fit Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Final Analysis of an International Randomized Study of the German CLL Study Group (GCLLSG) (CLL10 Study). ASH Annual Meeting Abstracts 2014.","DOI":"10.1182\/blood.V124.21.19.19"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-323980"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28292"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-547737"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-365437"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-329177"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.0442"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2009.07.008"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.199"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23983"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197303)31:3<502::AID-CNCR2820310303>3.0.CO;2-7"},{"key":"e_1_2_8_57_1","first-page":"329","article-title":"Biweekly chlorambucil treatment of lymphocytic lymphoma","volume":"3","author":"Knospe WH","year":"1980","journal-title":"Cancer Clin Trials"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-206185"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012143432402"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.9098"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.8389"},{"key":"e_1_2_8_62_1","unstructured":"EichhorstBF BahloJ BuschR et al.Longterm Follow\u2010up of a randomized phase III comparing fludarabine and chlorambucil in first line therapy of elderly patients with advanced chronic lymphocytic leukemia.2015. Publication submitted."},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1313984"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-1182"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.14"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.6547"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900632"},{"key":"e_1_2_8_68_1","doi-asserted-by":"crossref","unstructured":"HillmenP RobakT JanssensA et al.Ofatumumab + Chlorambucil Versus Chlorambucil Alone In Patients With Untreated Chronic Lymphocytic Leukemia (CLL): Results Of The Phase III Study Complement 1 (OMB110911). ASH Annual Meeting Abstracts 2013;122 (21).","DOI":"10.1182\/blood.V122.21.528.528"},{"key":"e_1_2_8_69_1","unstructured":"OffnerF PanagiotidisP AfanasyevB et al.Ofatumumab and bendamustine combination therapy in patients with untreated and relapsed chronic lymphocytic leukemia: initial results of the phase II study OMB115991. XV iwCLL Meeting Abstracts 2013:429 2013."},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.933217"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.2619"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-408047"},{"key":"e_1_2_8_73_1","first-page":"1","article-title":"Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose\u2010dense rituximab in elderly patients with chronic lymphocytic leukemia","volume":"14","author":"Dartigeas C","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"e_1_2_8_74_1","article-title":"A randomised dose de\u2010escalation study of oral fludarabine, \u00b1oral cyclophosphamide and intravenous rituximab as first\u2010line therapy of fit patients with chronic lymphocytic leukaemia (CLL) Aged =65 Years: final analysis of response and toxicity","volume":"124","author":"Mulligan S","year":"2014","journal-title":"Blood"},{"key":"e_1_2_8_75_1","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V124.21.4670.4670","article-title":"Low\u2010dose FCR is a safe and effective treatment option for Elderly\/Comorbid patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma. Updated results of project Q\u2010Lite By Czech CLL study group","volume":"124","author":"Smolej L","year":"2014","journal-title":"Blood"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.146"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404441"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.695781"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-352492"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-328484"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315226"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70335-3"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400376"},{"key":"e_1_2_8_84_1","doi-asserted-by":"crossref","unstructured":"O'BrienS JonesJA CoutreS et al.Efficacy and Safety of Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia with 17p Deletion: Results from the Phase II RESONATE\u2122\u201017 TrialClinically Relevant Abstract. ASH Annual Meeting Abstracts 2014.","DOI":"10.1182\/blood.V124.21.327.327"},{"key":"e_1_2_8_85_1","doi-asserted-by":"crossref","unstructured":"SharmanJP CoutreSE FurmanRR et al.Second Interim Analysis of a Phase 3 Study of Idelalisib (ZYDELIG\u00ae) Plus Rituximab (R) for Relapsed Chronic Lymphocytic Leukemia (CLL): Efficacy Analysis in Patient Subpopulations with Del(17p) and Other Adverse Prognostic Factors. ASH Annual Meeting Abstracts 2014.","DOI":"10.1182\/blood.V124.21.330.330"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_2_8_87_1","doi-asserted-by":"crossref","unstructured":"RobertsAW MaS BranderDM et al.Determination of Recommended Phase 2 Dose of ABT\u2010199 (GDC\u20100199) Combined with Rituximab (R) in Patients with Relapsed\/Refractory (R\/R) Chronic Lymphocytic Leukemia (CLL). ASH Annual Meeting Abstracts 2014.","DOI":"10.1182\/blood.V124.21.325.325"},{"key":"e_1_2_8_88_1","article-title":"Selective inhibition of bcl\u20102 is active against chronic lymphocytic leukemia (CLL): First clinical experience with the BH3\u2010mimetic ABT\u2010199","volume":"97","author":"Roberts A","year":"2012","journal-title":"Haematologica"},{"key":"e_1_2_8_89_1","doi-asserted-by":"crossref","unstructured":"SeymourJF DavidsMS PagelJM.ABT\u2010199 (GDC\u20100199) in relapsed\/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: high response rates among patients with high risk disease features including unmutated IGHV. Haematologica EHA Abstract 2014 2014.","DOI":"10.1200\/jco.2014.32.15_suppl.7015"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201007\u2010586826"},{"key":"e_1_2_8_91_1","doi-asserted-by":"crossref","unstructured":"GoedeV EngelkeA FischerK et al.Salvage Therapy with Obinutuzumab (GA101) Plus Chlorambucil (Clb) after Treatment Failure of Clb Alone in Patients with Chronic Lymphocytic Leukemia (CLL) and Comorbidities: Results of the CLL11 Study. ASH Annual Meeting Abstracts 2014.","DOI":"10.1182\/blood.V124.21.3327.3327"},{"key":"e_1_2_8_92_1","article-title":"Signaling the end of chronic lymphocytic leukemia?: new frontline treatment strategies","volume":"138","author":"Hallek M","year":"2013","journal-title":"Blood"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejh.12678","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.12678","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T15:39:26Z","timestamp":1695742766000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.12678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,6]]},"references-count":91,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1111\/ejh.12678"],"URL":"https:\/\/doi.org\/10.1111\/ejh.12678","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,6]]}}}