{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:18:09Z","timestamp":1783937889019,"version":"3.55.0"},"reference-count":64,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Bruton tyrosine kinase inhibitors improve outcomes for patients with chronic lymphocytic leukemia (CLL). Long-term data with continuous therapy are limited. With a median follow-up of 10.0 years, we report final results on 84 patients with TP53 aberrations (deletion of chromosomal arm 17p or TP53 mutation) or \u226565 years of age treated with 420 mg of single-agent ibrutinib daily until progression or unacceptable toxicity. A total of 52 (61.9%) patients were previously untreated; 56 (66.7%) had unmutated immunoglobulin heavy-chain variable region; and 53 (63.1%) had TP53 aberrations, including 34 treatment na\u00efve patients. As of 31July 2024, 9 (10.7%) patients continued ibrutinib, 39 (46.4%) discontinued ibrutinib for progressive disease, 31 (36.9%) for adverse events, and 5 (5.9%) withdrew consent. The median progression-free survival (PFS) was 7.2 years; median overall survival (OS) was not reached. In patients with and without TP53 aberrations, median PFS was 5.6 years and not reached, and 10-year OS was 51.3% and 75.3%, respectively. The estimated 10-year PFS and OS for patients with TP53-aberrant CLL treated in first line was 38.6% and 65.7%, respectively. Minimal residual disease (MRD) was quantified by peripheral blood flow cytometry annually. Undetectable MRD (uMRD; at 10\u22124) was achieved in 13 (15.5%) patients after a median of 5 years. Twelve patients maintained uMRD, the longest observation ongoing at 8.0 years. Seventeen (42.5%) patients with best response of high MRD (&amp;gt;10\u22122) remained progression-free for &amp;gt;5 years. These results highlight durable benefits and deepening responses with ibrutinib, including in high-risk CLL. Whether patients maintaining uMRD for years can safely discontinue therapy should be assessed prospectively. This trial was registered at www.clinicaltrials.gov as NCT01500733.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029971","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T15:18:01Z","timestamp":1765984681000},"page":"1702-1712","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["A decade of ibrutinib for CLL with and without\n                    <i>TP53<\/i>\n                    aberration: final report on an investigator-sponsored phase 2 study"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2385-3241","authenticated-orcid":false,"given":"Andy","family":"Itsara","sequence":"first","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6185-0776","authenticated-orcid":false,"given":"Victoria M.","family":"Rogness","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Samples","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2601-3665","authenticated-orcid":false,"given":"Constance M.","family":"Yuan","sequence":"additional","affiliation":[{"name":"2Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-9253","authenticated-orcid":false,"given":"Hao-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"2Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3717-287X","authenticated-orcid":false,"given":"Inhye E.","family":"Ahn","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"},{"name":"3Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Z. H.","family":"Farooqui","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-2462","authenticated-orcid":false,"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"4Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-4729","authenticated-orcid":false,"given":"Clare","family":"Sun","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Tomasulo","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"},{"name":"5Pennsylvania Hospital, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Soto","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine","family":"Superata","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Bezkorovaynaya","sequence":"additional","affiliation":[{"name":"6Office of the Clinical Director, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"7Department of Pharmacy, Clinical Research Center, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Nierman","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-2924","authenticated-orcid":false,"given":"Adrian","family":"Wiestner","sequence":"additional","affiliation":[{"name":"1Laboratory of Lymphoid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"12","key":"2026040911265678500_bib1","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.3324\/haematol.2014.119123","article-title":"The role of B-cell receptor inhibitors in the treatment of patients with chronic lymphocytic leukemia","volume":"100","author":"Wiestner","year":"2015","journal-title":"Haematologica"},{"issue":"3","key":"2026040911265678500_bib2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nrc.2017.121","article-title":"Targeting B cell receptor signalling in cancer: preclinical and clinical advances","volume":"18","author":"Burger","year":"2018","journal-title":"Nat Rev Cancer"},{"issue":"21","key":"2026040911265678500_bib3","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1182\/blood-2014-02-548610","article-title":"Ibrutinib inhibits BCR and NF-kB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL","volume":"123","author":"Herman","year":"2014","journal-title":"Blood"},{"issue":"1","key":"2026040911265678500_bib4","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1038\/s41467-017-02329-y","article-title":"The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy","volume":"8","author":"Landau","year":"2017","journal-title":"Nat Commun"},{"issue":"6","key":"2026040911265678500_bib5","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1182\/blood-2012-02-362624","article-title":"The B-cell receptor signaling pathway as a therapeutic target in CLL","volume":"120","author":"Woyach","year":"2012","journal-title":"Blood"},{"issue":"1","key":"2026040911265678500_bib6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1215637","article-title":"Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia","volume":"369","author":"Byrd","year":"2013","journal-title":"N Engl J Med"},{"issue":"3","key":"2026040911265678500_bib7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1400376","article-title":"Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia","volume":"371","author":"Byrd","year":"2014","journal-title":"N Engl J Med"},{"issue":"25","key":"2026040911265678500_bib8","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia","volume":"373","author":"Burger","year":"2015","journal-title":"N Engl J Med"},{"issue":"5","key":"2026040911265678500_bib9","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1056\/NEJMoa1817073","article-title":"Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia","volume":"381","author":"Shanafelt","year":"2019","journal-title":"N Engl J Med"},{"issue":"1","key":"2026040911265678500_bib10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1470-2045(18)30788-5","article-title":"Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial","volume":"20","author":"Moreno","year":"2019","journal-title":"Lancet Oncol"},{"issue":"31","key":"2026040911265678500_bib11","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial","volume":"39","author":"Byrd","year":"2021","journal-title":"J Clin Oncol"},{"issue":"4","key":"2026040911265678500_bib12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia","volume":"388","author":"Brown","year":"2023","journal-title":"N Engl J Med"},{"issue":"8","key":"2026040911265678500_bib13","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1182\/blood.2022018818","article-title":"Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial","volume":"142","author":"Seymour","year":"2023","journal-title":"Blood"},{"issue":"26","key":"2026040911265678500_bib14","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1182\/blood.2024024667","article-title":"Sustained benefit of zanubrutinib vs ibrutinib in patients with R\/R CLL\/SLL: final comparative analysis of ALPINE","volume":"144","author":"Brown","year":"2024","journal-title":"Blood"},{"issue":"1","key":"2026040911265678500_bib15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1200\/JCO.2012.42.7906","article-title":"Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed\/refractory B-cell malignancies","volume":"31","author":"Advani","year":"2013","journal-title":"J Clin Oncol"},{"issue":"29","key":"2026040911265678500_bib16","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1200\/JCO.2009.27.8762","article-title":"TP53 mutation and survival in chronic lymphocytic leukemia","volume":"28","author":"Zenz","year":"2010","journal-title":"J Clin Oncol"},{"issue":"16","key":"2026040911265678500_bib17","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1200\/JCO.2010.32.0838","article-title":"Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial","volume":"29","author":"Gonzalez","year":"2011","journal-title":"J Clin Oncol"},{"issue":"21","key":"2026040911265678500_bib18","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1182\/blood-2014-01-546150","article-title":"Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial","volume":"123","author":"Stilgenbauer","year":"2014","journal-title":"Blood"},{"issue":"16","key":"2026040911265678500_bib19","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1182\/blood.2023021959","article-title":"Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL","volume":"143","author":"Woyach","year":"2024","journal-title":"Blood"},{"issue":"21","key":"2026040911265678500_bib20","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1182\/blood-2017-12-820910","article-title":"Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study","volume":"131","author":"Ahn","year":"2018","journal-title":"Blood"},{"issue":"6","key":"2026040911265678500_bib21","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1200\/JCO.20.00979","article-title":"Prediction of outcome in patients with chronic lymphocytic leukemia treated with ibrutinib: development and validation of a four-factor prognostic model","volume":"39","author":"Ahn","year":"2021","journal-title":"J Clin Oncol"},{"issue":"5","key":"2026040911265678500_bib22","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1056\/NEJMc2005943","article-title":"Ibrutinib for chronic lymphocytic leukemia with TP53 alterations","volume":"383","author":"Ahn","year":"2020","journal-title":"N Engl J Med"},{"issue":"2","key":"2026040911265678500_bib23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/blood-2015-06-651125","article-title":"Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial","volume":"127","author":"Fischer","year":"2016","journal-title":"Blood"},{"issue":"18","key":"2026040911265678500_bib24","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1182\/blood.2024024631","article-title":"Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study","volume":"144","author":"Al-Sawaf","year":"2024","journal-title":"Blood"},{"issue":"12","key":"2026040911265678500_bib25","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S1470-2045(23)00452-7","article-title":"Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial","volume":"24","author":"Niemann","year":"2023","journal-title":"Lancet Oncol"},{"issue":"4","key":"2026040911265678500_bib26","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1056\/NEJMoa2310063","article-title":"Chronic lymphocytic leukemia therapy guided by measurable residual disease","volume":"390","author":"Munir","year":"2024","journal-title":"N Engl J Med"},{"issue":"8","key":"2026040911265678500_bib27","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1056\/NEJMoa2409804","article-title":"Fixed-duration acalabrutinib combinations in untreated chronic lymphocytic leukemia","volume":"392","author":"Brown","year":"2025","journal-title":"N Engl J Med"},{"issue":"19","key":"2026040911265678500_bib28","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1056\/NEJMoa2213093","article-title":"First-line venetoclax combinations in chronic lymphocytic leukemia","volume":"388","author":"Eichhorst","year":"2023","journal-title":"N Engl J Med"},{"issue":"2","key":"2026040911265678500_bib29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1470-2045(14)71182-9","article-title":"Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial","volume":"16","author":"Farooqui","year":"2015","journal-title":"Lancet Oncol"},{"issue":"25","key":"2026040911265678500_bib30","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"issue":"1","key":"2026040911265678500_bib31","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/leu.2012.216","article-title":"Improving efficiency and sensitivity: European Research Initiative in CLL (ERIC) update on the international harmonised approach for flow cytometric residual disease monitoring in CLL","volume":"27","author":"Rawstron","year":"2013","journal-title":"Leukemia"},{"issue":"16","key":"2026040911265678500_bib32","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1158\/1078-0432.CCR-20-4890","article-title":"Clinical outcomes in patients with multi-hit TP53 chronic lymphocytic leukemia treated with ibrutinib","volume":"27","author":"Brieghel","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"12","key":"2026040911265678500_bib33","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1182\/bloodadvances.2018028761","article-title":"Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies","volume":"3","author":"Coutre","year":"2019","journal-title":"Blood Adv"},{"issue":"15","key":"2026040911265678500_bib34","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1182\/blood.2018884940","article-title":"Acalabrutinib monotherapy in patients with relapsed\/refractory chronic lymphocytic leukemia: updated phase 2 results","volume":"135","author":"Byrd","year":"2020","journal-title":"Blood"},{"issue":"17","key":"2026040911265678500_bib35","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1182\/blood-2017-10-810044","article-title":"Single-agent ibrutinib in treatment-naive and relapsed\/refractory chronic lymphocytic leukemia: a 5-year experience","volume":"131","author":"O'Brien","year":"2018","journal-title":"Blood"},{"issue":"13","key":"2026040911265678500_bib36","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1182\/bloodadvances.2023011307","article-title":"Acalabrutinib-based regimens in frontline or relapsed\/refractory higher-risk CLL: pooled analysis of 5 clinical trials","volume":"8","author":"Davids","year":"2024","journal-title":"Blood Adv"},{"issue":"5","key":"2026040911265678500_bib37","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/ajh.25436","article-title":"Outcomes with ibrutinib by line of therapy and post-ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis","volume":"94","author":"O'Brien","year":"2019","journal-title":"Am J Hematol"},{"issue":"11","key":"2026040911265678500_bib38","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.3324\/haematol.2021.280376","article-title":"A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib","volume":"107","author":"Mato","year":"2022","journal-title":"Haematologica"},{"issue":"12","key":"2026040911265678500_bib39","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/ajh.25638","article-title":"Final analysis from RESONATE: up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma","volume":"94","author":"Munir","year":"2019","journal-title":"Am J Hematol"},{"issue":"11","key":"2026040911265678500_bib40","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1182\/bloodadvances.2021006434","article-title":"Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia","volume":"6","author":"Barr","year":"2022","journal-title":"Blood Adv"},{"issue":"1","key":"2026040911265678500_bib41","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1182\/bloodadvances.2024013474","article-title":"Tolerability and long-term disease control by IGHV mutation status among patients with CLL on ibrutinib arm of E1912","volume":"9","author":"Shanafelt","year":"2025","journal-title":"Blood Adv"},{"issue":"1","key":"2026040911265678500_bib42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1182\/blood.2019003715","article-title":"Clinical and biological implications of target occupancy in CLL treated with the BTK inhibitor acalabrutinib","volume":"136","author":"Sun","year":"2020","journal-title":"Blood"},{"issue":"8","key":"2026040911265678500_bib43","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1080\/03007995.2024.2368175","article-title":"Overall survival of patients with CLL treated with ibrutinib in the first line compared to second-line ibrutinib after chemotherapy\/chemoimmunotherapy","volume":"40","author":"Robak","year":"2024","journal-title":"Curr Med Res Opin"},{"issue":"3","key":"2026040911265678500_bib44","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41375-019-0602-x","article-title":"Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL\/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study","volume":"34","author":"Burger","year":"2020","journal-title":"Leukemia"},{"issue":"10","key":"2026040911265678500_bib45","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1080\/10428194.2020.1772477","article-title":"Reconstitution of humoral immunity and decreased risk of infections in patients with chronic lymphocytic leukemia treated with Bruton tyrosine kinase inhibitors","volume":"61","author":"Pleyer","year":"2020","journal-title":"Leuk Lymphoma"},{"issue":"5","key":"2026040911265678500_bib46","doi-asserted-by":"crossref","first-page":"874","DOI":"10.3324\/haematol.2017.182907","article-title":"Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis","volume":"103","author":"Mato","year":"2018","journal-title":"Haematologica"},{"issue":"9","key":"2026040911265678500_bib47","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1200\/JCO.2011.36.9348","article-title":"Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial","volume":"30","author":"B\u00f6ttcher","year":"2012","journal-title":"J Clin Oncol"},{"issue":"1","key":"2026040911265678500_bib48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1182\/blood.V98.1.29","article-title":"Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy","volume":"98","author":"Rawstron","year":"2001","journal-title":"Blood"},{"issue":"21","key":"2026040911265678500_bib49","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1200\/JCO.22.02283","article-title":"Impact of minimal residual disease on progression-free survival outcomes after fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in the GLOW study","volume":"41","author":"Munir","year":"2023","journal-title":"J Clin Oncol"},{"issue":"34","key":"2026040911265678500_bib50","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1200\/JCO.21.00807","article-title":"Ibrutinib plus venetoclax for first-line treatment of chronic lymphocytic leukemia: primary analysis results from the minimal residual disease cohort of the randomized phase II CAPTIVATE study","volume":"39","author":"Wierda","year":"2021","journal-title":"J Clin Oncol"},{"issue":"16","key":"2026040911265678500_bib51","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1158\/1078-0432.CCR-22-3887","article-title":"B-cell receptor pathway mutations are infrequent in patients with chronic lymphocytic leukemia on continuous ibrutinib therapy","volume":"29","author":"Woyach","year":"2023","journal-title":"Clin Cancer Res"},{"issue":"4","key":"2026040911265678500_bib52","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/s41375-021-01485-x","article-title":"Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-na\u00efve chronic lymphocytic leukemia","volume":"36","author":"Sharman","year":"2022","journal-title":"Leukemia"},{"issue":"4","key":"2026040911265678500_bib53","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/bjh.17984","article-title":"Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials","volume":"196","author":"Allan","year":"2022","journal-title":"Br J Haematol"},{"issue":"9","key":"2026040911265678500_bib54","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.3324\/haematol.2020.259432","article-title":"Zanubrutinib monotherapy for patients with treatment na\u00efve chronic lymphocytic leukemia and 17p deletion","volume":"106","author":"Tam","year":"2021","journal-title":"Haematologica"},{"issue":"24","key":"2026040911265678500_bib55","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1182\/blood.2021012315","article-title":"Ibrutinib induces durable remissions in treatment-na\u00efve patients with CLL and 17p deletion and\/or TP53 mutations","volume":"138","author":"Sivina","year":"2021","journal-title":"Blood"},{"issue":"10","key":"2026040911265678500_bib56","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S1470-2045(16)30212-1","article-title":"Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study","volume":"17","author":"O'Brien","year":"2016","journal-title":"Lancet Oncol"},{"issue":"10","key":"2026040911265678500_bib57","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1182\/blood-2018-10-879429","article-title":"Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia","volume":"133","author":"Burger","year":"2019","journal-title":"Blood"},{"issue":"14","key":"2026040911265678500_bib58","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1158\/1078-0432.CCR-22-2779","article-title":"Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: phase II CAPTIVATE study in first-line chronic lymphocytic leukemia","volume":"29","author":"Allan","year":"2023","journal-title":"Clin Cancer Res"},{"issue":"21","key":"2026040911265678500_bib59","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1200\/JCO-25-00758","article-title":"Zanubrutinib and venetoclax for patients with treatment-na\u00efve chronic lymphocytic leukemia\/small lymphocytic lymphoma with and without Del(17p)\/TP53 mutation: SEQUOIA arm D results","volume":"43","author":"Shadman","year":"2025","journal-title":"J Clin Oncol"},{"issue":"11","key":"2026040911265678500_bib60","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1182\/blood.2023020013","article-title":"Final analysis of the CLL2-GIVe trial: obinutuzumab, ibrutinib, and venetoclax for untreated CLL with del(17p)\/TP53mut","volume":"142","author":"Huber","year":"2023","journal-title":"Blood"},{"issue":"7","key":"2026040911265678500_bib61","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1200\/JCO-24-02503","article-title":"Phase II study of acalabrutinib, venetoclax, and obinutuzumab in a treatment-na\u00efve chronic lymphocytic leukemia population enriched for high-risk disease","volume":"43","author":"Davids","year":"2025","journal-title":"J Clin Oncol"},{"issue":"1","key":"2026040911265678500_bib62","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1182\/bloodadvances.2021006941","article-title":"The immune microenvironment shapes transcriptional and genetic heterogeneity in chronic lymphocytic leukemia","volume":"7","author":"Sun","year":"2023","journal-title":"Blood Adv"},{"issue":"7","key":"2026040911265678500_bib63","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/s41375-023-01901-4","article-title":"Venetoclax consolidation in high-risk CLL treated with ibrutinib for \u22651 year achieves a high rate of undetectable MRD","volume":"37","author":"Thompson","year":"2023","journal-title":"Leukemia"},{"issue":"3","key":"2026040911265678500_bib64","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1158\/1078-0432.CCR-22-3934","article-title":"Absence of BTK, BCL2, and PLCG2 mutations in chronic lymphocytic leukemia relapsing after first-line treatment with fixed-duration ibrutinib plus venetoclax","volume":"30","author":"Jain","year":"2024","journal-title":"Clin Cancer Res"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/15\/1702\/2512094\/blood_bld-2025-029971-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/15\/1702\/2512094\/blood_bld-2025-029971-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:27:12Z","timestamp":1775748432000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/147\/15\/1702\/557374\/A-decade-of-ibrutinib-for-CLL-with-and-without"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":64,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,4,9]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2025029971","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4,9]]},"published":{"date-parts":[[2026,4,9]]}}}