{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:14:02Z","timestamp":1792840442526,"version":"4.5.0"},"reference-count":38,"publisher":"American Society of Hematology","issue":"2","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib\u2013rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-na\u00efve patients aged \u226470 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P &amp;lt; .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P &amp;lt; .001) and IGHV unmutated CLL (HR: 0.27; P &amp;lt; .001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events (AEs)\/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813.<\/jats:p>","DOI":"10.1182\/blood.2021014960","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T15:17:07Z","timestamp":1650035827000},"page":"112-120","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":239,"title":["Long-term outcomes for ibrutinib\u2013rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial"],"prefix":"10.1182","volume":"140","author":[{"given":"Tait D.","family":"Shanafelt","sequence":"first","affiliation":[{"name":"1Stanford University, Stanford, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin Victoria","family":"Wang","sequence":"additional","affiliation":[{"name":"2Dana Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis A.","family":"Hanson","sequence":"additional","affiliation":[{"name":"3Mayo Clinic, Rochester, MN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"Paietta","sequence":"additional","affiliation":[{"name":"4Montefiore Medical Center, Bronx, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-7504","authenticated-orcid":false,"given":"Susan","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"5University of California Irvine Medical Center, Irvine, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Barrientos","sequence":"additional","affiliation":[{"name":"6Northwell Health\/Center for Advanced Medicine, New Hyde Park, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane F.","family":"Jelinek","sequence":"additional","affiliation":[{"name":"3Mayo Clinic, Rochester, MN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-4830","authenticated-orcid":false,"given":"Esteban","family":"Braggio","sequence":"additional","affiliation":[{"name":"3Mayo Clinic, Rochester, MN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose F.","family":"Leis","sequence":"additional","affiliation":[{"name":"3Mayo Clinic, Rochester, MN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong Christine","family":"Zhang","sequence":"additional","affiliation":[{"name":"7Kaiser Permanente NCORP\/The Permanente Medical Group, Fresno, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Coutre","sequence":"additional","affiliation":[{"name":"1Stanford University, Stanford, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-401X","authenticated-orcid":false,"given":"Paul M.","family":"Barr","sequence":"additional","affiliation":[{"name":"8Rochester University, Rochester, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda F.","family":"Cashen","sequence":"additional","affiliation":[{"name":"9Washington University School of Medicine, St. Louis, MO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Mato","sequence":"additional","affiliation":[{"name":"10Memorial Sloan-Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avina K.","family":"Singh","sequence":"additional","affiliation":[{"name":"11Minnesota Oncology, Burnsville, MN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Mullane","sequence":"additional","affiliation":[{"name":"12Aurora Cancer Care, Milwaukee West, Milwaukee, 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