{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:14:29Z","timestamp":1793650469925,"version":"4.5.1"},"reference-count":19,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>With up to 10 years of follow-up, we report results from the final analysis of RESONATE- 2, a phase 3 study of first-line ibrutinib vs chlorambucil for the treatment of chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL). Patients aged \u226565 years with previously untreated CLL\/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg\/d; n = 136) or chlorambucil (0.5-0.8 mg\/kg; \u226412 cycles; n = 133). With a median follow-up of 9.6 years in the ibrutinib arm, the median progression-free survival (PFS) was 8.9 years (95% confidence interval [CI], 7.0 to not estimable [NE]) vs 1.3 years (95% CI, 0.9-1.6) for the chlorambucil arm. Among patients with unmutated immunoglobulin heavy chain variable (uIGHV), del (11q), mutated TP53, or complex karyotype, the median PFS was 8.4 years (95% CI, 6.8 to NE) with ibrutinib and 0.7 years (95% CI, 0.4-1.2) with chlorambucil. Median overall survival (OS) with ibrutinib was not reached. The most common adverse events (AEs) of any grade included diarrhea (52%), fatigue (41%), cough (39%), nausea (32%), arthralgia (31%), peripheral edema (31%), and hypertension (30%). During the entire study period, 34 of 136 patients (25%) had an ibrutinib dose reduction due to AEs; these AEs improved in 30 of 34 patients (88%). At study completion, 27% of patients remained on first-line ibrutinib treatment. This landmark RESONATE-2 study defines median PFS and demonstrates continued OS benefit of first-line ibrutinib treatment for patients with CLL\/SLL, including those with high-risk genomic features. Sustained efficacy and tolerability of ibrutinib reemphasize the favorable benefit-risk profile. This trial was registered at www.ClinicalTrials.gov as NCT01722487\/NCT01724346.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024028205","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T20:15:58Z","timestamp":1753906558000},"page":"2168-2176","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":45,"title":["Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL\/SLL"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-7572","authenticated-orcid":false,"given":"Jan A.","family":"Burger","sequence":"first","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"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":"2Department of Medicine, Hematology, and Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-6357","authenticated-orcid":false,"given":"Tadeusz","family":"Robak","sequence":"additional","affiliation":[{"name":"3Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Owen","sequence":"additional","affiliation":[{"name":"4Division of Hematology and Hematological Malignancies, Tom Baker Cancer Centre, University of Calgary, Calgary, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"5Department of Hematology, Niguarda Ca\u2019 Granda Hospital, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Sarma","sequence":"additional","affiliation":[{"name":"6Department of Haematology, St. James's University Hospital, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3320-3034","authenticated-orcid":false,"given":"Piers E. 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