{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:48:59Z","timestamp":1790711339189,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T00:00:00Z","timestamp":1584489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014491","name":"Pharmacyclics.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014491","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To study the impact of dose modification and temporary interruption of ibrutinib in routine clinical practice, we conducted a retrospective study of consecutive CLL patients treated with ibrutinib outside the context of a clinical trial at Mayo Clinic, (Rochester, MN) from 11\/2013 to 12\/2017. Of 209 patients, 131 (74%) had unmutated\n                    <jats:italic>IGHV<\/jats:italic>\n                    , 38 (20%) had\n                    <jats:italic>TP53<\/jats:italic>\n                    disruption, and 47 (22%) were previously untreated. A total of 87\/209 (42%) patients started reduced dose ibrutinib (&lt;420\u00a0mg daily; n\u00a0=\u00a043, physician preference; n\u00a0=\u00a033, concomitant medications; and n\u00a0=\u00a011, other). During 281 person\u2010years of treatment, 91\/209 patients had temporary dose interruption (54%, nonhematologic toxicity; 29%, surgical procedures; 10%, hematologic toxicity; and 7%, other). After a median follow\u2010up of 24\u00a0months, the estimated median event\u2010free survival (EFS) was 36\u00a0months, and median overall survival (OS) was not reached. On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.006) and\n                    <jats:italic>TP53<\/jats:italic>\n                    disruption at ibrutinib initiation (HR: 1.81,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.048) were associated with shorter EFS, whereas only\n                    <jats:italic>TP53<\/jats:italic>\n                    disruption (HR: 2.38,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.015) was associated with shorter OS. Initial ibrutinib dose and dose modification during therapy did not appear to impact EFS or OS. These findings illustrate the challenges associated with continuous oral therapy with ibrutinib in patients with CLL.\n                  <\/jats:p>","DOI":"10.1002\/cam4.2998","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T17:00:32Z","timestamp":1584550832000},"page":"3390-3399","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-7314","authenticated-orcid":false,"given":"Sameer A.","family":"Parikh","sequence":"first","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J.","family":"Achenbach","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics &amp; Informatics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Call","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari G.","family":"Rabe","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics &amp; Informatics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9811-4601","authenticated-orcid":false,"given":"Wei","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose F.","family":"Leis","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Mayo Clinic Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2767-3830","authenticated-orcid":false,"given":"Saad S.","family":"Kenderian","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher A.","family":"Chanan\u2010Khan","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Mayo Clinic Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2539-040X","authenticated-orcid":false,"given":"Amber B.","family":"Koehler","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Schwager","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Muchtar","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amie L.","family":"Fonder","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen B.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne N.","family":"Nedved","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Slager","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics &amp; Informatics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil E.","family":"Kay","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1117-0983","authenticated-orcid":false,"given":"Heidi D.","family":"Finnes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tait D.","family":"Shanafelt","sequence":"additional","affiliation":[{"name":"Division of Hematology Stanford University School of Medicine Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509388"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400376"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215637"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-810044"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-737346"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2016.1251592"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.182907"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23939"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12458"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.086066"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25292"},{"key":"e_1_2_9_13_1","unstructured":"IMBRUVICA\u00ae [package insert].Sunnyvale CA:Pharmacyclics. Inc. February 2014. (Accessed May 25 2018 athttp:\/\/www.imbruvica.com\/cll)."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14332"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.42.7906"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-06-860593"},{"key":"e_1_2_9_17_1","first-page":"427","article-title":"Randomized trial of ibrutinib versus ibrutinib plus rituximab (Ib+R) in patients with Chronic Lymphocytic Leukemia (CLL)","volume":"130","author":"Burger JA","year":"2017","journal-title":"Blood"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812836"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30788-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1815281"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900574"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.2998","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2998","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.2998","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T21:07:48Z","timestamp":1693948068000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.2998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,18]]},"references-count":20,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/cam4.2998"],"URL":"https:\/\/doi.org\/10.1002\/cam4.2998","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,18]]},"assertion":[{"value":"2019-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}