{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:12:32Z","timestamp":1793142752212,"version":"4.5.0"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A major revolution in the treatment of chronic lymphocytic leukemia (CLL) began with the approval of ibrutinib, a first\u2010in\u2010class oral inhibitor of Bruton tyrosine kinase (BTK), for the treatment of relapsed\/refractory (R\/R) and\/or TP53 mutated patients with CLL. However, 5\u2009years later, some issues relating to this disorder still remain including the fact that with ibrutinib only a relatively small proportion of patients achieve complete remission and that ibrutinib\u2010resistant CLL clones can develop in about 20% of patients. In addition, therapy must still be given continuously, and toxicities leading to drug discontinuation occur in about 30% of patients. In the meantime second\u2010generation BTK inhibitors have already aroused considerable interest and gathered momentum. A possible strategy to overcome some of these obstacles is to combine ibrutinib with other targeted agents especially in high\u2010risk disease, such as previously treated refractory patients or those with TP53 aberrations or complex karyotypes, in whom rapid eradication of disease is most desirable. Therapy with single agent ibrutinib should be part of a sequential approach for patients with low risk disease, especially in older patients (aged &gt;70\u2009years) with a higher burden of comorbidities. Long\u2010term results of ongoing studies combining Ibrutinib with (chemo)\u2010immunotherapy or other targeted agents are eagerly awaited. Future clinical trials are indeed still needed to provide answers to these open questions.<\/jats:p>","DOI":"10.1002\/hon.2695","type":"journal-article","created":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T01:34:23Z","timestamp":1573868063000},"page":"129-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Ibrutinib in the treatment of chronic lymphocytic leukemia: 5\u2009years on"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-6507","authenticated-orcid":false,"given":"Stefano","family":"Molica","sequence":"first","affiliation":[{"name":"Department of Hematology\u2010Oncology Azienda Ospedaliera Pugliese\u2010Ciaccio  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estella","family":"Matutes","sequence":"additional","affiliation":[{"name":"Haematopathology Unit, Hospital Clinic Barcelona University  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine","family":"Tam","sequence":"additional","affiliation":[{"name":"St Vincent's Hospital Peter MacCallum Cancer Centre and University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Polliack","sequence":"additional","affiliation":[{"name":"Department of Hematology Hadassah\u2010Hebrew\u2010University Medical Center  Jerusalem 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Five\u2010year follow\u2010up of patients receiving ibrutinib for first\u2010line treatment of chronic lymphocytic leukemia. Paper presented at: 2019 European Hematology Association Congress; June 13\u201016 2019; Amsterdam Netherlands. 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ASCEND phase 3 study of acalabrutinib vs investigator's choice of rituximab plus idelasib (IDR) or bendamustine (BR) in patients with relapsed\/refractory (R\/R) chronic lymphocytic leukemia (CLL). Paper presented at: 2019 European Hematology Association Congress; June 13\u201316 2019; Amsterdam Netherlands. Abstract LB2606.","DOI":"10.1002\/hon.54_2629"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01580"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018882555"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001189"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25457"},{"key":"e_1_2_11_69_1","doi-asserted-by":"crossref","unstructured":"LangerbeinsP BahloJ RheinC et al. 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