{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:29:37Z","timestamp":1776274177715,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:00:00Z","timestamp":1539043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Pharmacyclics LLC, an AbbVie Company"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemoimmunotherapy (CIT) and targeted therapy with single\u2010agent ibrutinib are both recommended first\u2010line treatments for chronic lymphocytic leukemia (CLL), although their outcomes have not been directly compared. Using ibrutinib data from the RESONATE\u20102 (PCYC\u20101115\/1116) study conducted in patients \u226565\u2009years without del(17p), we performed a cross\u2010trial comparison with CIT data from published phase 3 studies in first\u2010line treatment of CLL. Progression\u2010free survival (PFS), overall survival (OS), and safety data for ibrutinib (median follow\u2010up 35.7\u2009months) were evaluated alongside available CIT data. CIT regimens included: fludarabine + cyclophosphamide + rituximab (CLL8, CLL10), bendamustine + rituximab (CLL10), obinutuzumab + chlorambucil and rituximab + chlorambucil (CLL11), and ofatumumab + chlorambucil (COMPLEMENT\u20101). Median age across studies was 61\u201074\u2009years, with older populations receiving ibrutinib, obinutuzumab + chlorambucil, or rituximab + chlorambucil. Median follow\u2010up varied across studies\/regimens (range 14.5\u201037.4 months). Among all patients, PFS appeared longer with ibrutinib relative to CIT and OS appeared comparable. Relative to CIT studies that similarly excluded patients with del(17p) (CLL10) or enrolled older\/less\u2010fit patients (CLL11), PFS appeared favorable for ibrutinib in high\u2010risk subgroups, including advanced disease, bulky lymph nodes, unmutated <jats:italic>IGHV<\/jats:italic> status, and presence of del(11q). Grade\u2009\u2265\u20093 infections ranged from 9% (ofatumumab + chlorambucil) to 40% (fludarabine + cyclophosphamide + rituximab), and was 25% with ibrutinib. Grade\u2009\u2265\u20093 neutropenia was 12% for ibrutinib and 26%\u201084% for CIT. Although definitive conclusions cannot be made due to inherent limitations of cross\u2010trial comparisons, this report suggests that ibrutinib has a favorable benefit\/risk profile and may potentially eliminate the need for chemotherapy in some patients. Randomized, comparative studies are needed to support these findings.<\/jats:p>","DOI":"10.1002\/ajh.25259","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:26:53Z","timestamp":1534951613000},"page":"1402-1410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Single\u2010agent ibrutinib versus chemoimmunotherapy regimens for treatment\u2010na\u00efve patients with chronic lymphocytic leukemia: A cross\u2010trial comparison of phase 3 studies"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-6357","authenticated-orcid":false,"given":"Tadeusz","family":"Robak","sequence":"first","affiliation":[{"name":"Medical University of Lodz, Copernicus Memorial Hospital  Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan A.","family":"Burger","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"ASST Grande Ospedale Metropolitano Niguarda  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Barr","sequence":"additional","affiliation":[{"name":"Wilmot Cancer Institute, University of Rochester Cancer Center  Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Owen","sequence":"additional","affiliation":[{"name":"Tom Baker Cancer Centre University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osnat","family":"Bairey","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Beilinson Hospital and Sackler Faculty of Medicine Tel Aviv University  Tel Aviv 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A.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Norton Cancer Institute  Louisville Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Moreno","sequence":"additional","affiliation":[{"name":"Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devinder S.","family":"Gill","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital  Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian W.","family":"Flinn","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute\/Tennessee Oncology  Nashville Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"Gribben","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London  London 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