{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:09:33Z","timestamp":1786417773528,"version":"build-2736575974"},"reference-count":26,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,13]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Venetoclax-obinutuzumab (Ven-Obi) is a standard first-line therapy for chronic lymphocytic leukemia (CLL). The impact of age, fitness, and dose reductions remains unclear. We analyzed patients treated with Ven-Obi in the CLL13 and CLL14 trials, excluding patients with TP53 aberrations. Fitness was assessed using the cumulative illness rating scale (CIRS, &amp;gt;6) and creatinine clearance (\u226470 mL\/min). Among 410 patients (median age, 67 years), 55.7% were unfit (median age, 72 years) and 44.3% were fit (median age, 58 years). Overall response rate (ORR) was 89.5% in unfit and 96.1% in fit patients. Rates of undetectable minimal residual disease (uMRD) at &amp;lt;10\u20134 were 80.3% in unfit and 85.1% in fit patients. Progression-free survival (PFS) at 3 years was 86.4% vs 87.5% (hazard ratio, [HR], 1.12; 95% confidence interval [CI], 0.70-1.81; P = .63). Overall survival at 3 years was 91.8% vs 96.9% (HR, 2.02; 95% CI, 0.90-4.55; P = .088). Adverse events included neutropenia (62.7% unfit, 56.9% fit), infusion-related-reactions (44.3% unfit, 56.9% fit), fatigue (15.8% unfit, 35.9% fit), and infections (57.5% unfit, 69.6% fit). Venetoclax dose reductions of &amp;lt;80% occurred in 39.6% of unfit and 17.6% of fit patients, with lower ORR (83.3% vs 98.2%) and uMRD rates (74.2% vs 87.9%) in those with reduced dose intensities, but similar PFS. Dose reductions of &amp;lt;70% were associated with shorter PFS. Overall, this study shows comparable efficacy and toxicity of Ven-Obi in fit and unfit patients with CLL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025028899","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T19:21:06Z","timestamp":1756322466000},"page":"2406-2416","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["The impact of fitness and dose intensity on clinical outcomes with venetoclax-obinutuzumab in CLL"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-0570","authenticated-orcid":false,"given":"Othman","family":"Al-Sawaf","sequence":"first","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-0140","authenticated-orcid":false,"given":"Moritz","family":"F\u00fcrstenau","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Giza","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-6655","authenticated-orcid":false,"given":"Sandra","family":"Robrecht","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-4603","authenticated-orcid":false,"given":"Julia","family":"von Tresckow","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Oncology and Palliative Care, Katholisches Klinikum Bochum, Ruhr University Bochum, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Maria","family":"Fink","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2700-3717","authenticated-orcid":false,"given":"Florian","family":"Simon","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Tausch","sequence":"additional","affiliation":[{"name":"3Division of Chronic Lymphocytic Leukaemia, Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Schneider","sequence":"additional","affiliation":[{"name":"3Division of Chronic Lymphocytic Leukaemia, Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliya","family":"Sivcheva","sequence":"additional","affiliation":[{"name":"4First Department of Internal Medicine, Hristo Botev Multiprofile Hospital for Active Treatment, Vratsa, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Schwarer","sequence":"additional","affiliation":[{"name":"5Department of Haematology, Box Hill Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3561-3758","authenticated-orcid":false,"given":"Javier","family":"Loscertales","sequence":"additional","affiliation":[{"name":"6Hematology Department, Hospital De La Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3645-7988","authenticated-orcid":false,"given":"Robert","family":"Weinkove","sequence":"additional","affiliation":[{"name":"7Te Rerenga Ora Wellington Blood and Cancer Centre, Te Whatu Ora Health New Zealand Capital, Wellington, New Zealand"},{"name":"8Cancer Immunotherapy Program, Malaghan Institute of Medical Research, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Strumberg","sequence":"additional","affiliation":[{"name":"9Medical Department III, Hematology\/Oncology, Marien Hospital Herne, University Hospitals of the Ruhr University Bochum, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allanah","family":"Kilfoyle","sequence":"additional","affiliation":[{"name":"10Haematology Department, Palmerston North Hospital, Palmerston North, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Juliusson","sequence":"additional","affiliation":[{"name":"11Department of Haematology, Lund University Cancer Center, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-3098","authenticated-orcid":false,"given":"Caspar","family":"da Cunha-Bang","sequence":"additional","affiliation":[{"name":"12Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Illmer","sequence":"additional","affiliation":[{"name":"13Praxis of Haematology and Oncology, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gregor","sequence":"additional","affiliation":[{"name":"14Division of Hematology, Cantonal Hospital of Lucerne, Lucerne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Thornton","sequence":"additional","affiliation":[{"name":"15Department of Haematology, Beaumont Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1812-412X","authenticated-orcid":false,"given":"Ann","family":"Janssens","sequence":"additional","affiliation":[{"name":"16Department of Oncology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8612","authenticated-orcid":false,"given":"Tamar","family":"Tadmor","sequence":"additional","affiliation":[{"name":"17Deoartment of Hematology, Bnai-Zion Medical Center, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesa","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"18Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-7708","authenticated-orcid":false,"given":"Philipp","family":"Staber","sequence":"additional","affiliation":[{"name":"19Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-3547","authenticated-orcid":false,"given":"Mark-David","family":"Levin","sequence":"additional","affiliation":[{"name":"20Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens-Martin","family":"Wendtner","sequence":"additional","affiliation":[{"name":"21Department of Medicine III and Comprehensive Cancer Center (Munich), Ludwig-Maximilians University Hospital, Ludwig Maximilian University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Anton","family":"Kreuzer","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ritgen","sequence":"additional","affiliation":[{"name":"22Department II of Internal Medicine, University of Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Stilgenbauer","sequence":"additional","affiliation":[{"name":"3Division of Chronic Lymphocytic Leukaemia, Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3190-1891","authenticated-orcid":false,"given":"Arnon P.","family":"Kater","sequence":"additional","affiliation":[{"name":"23Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9880-5242","authenticated-orcid":false,"given":"Carsten","family":"Niemann","sequence":"additional","affiliation":[{"name":"24Department of Hematology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Eichhorst","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7425-4455","authenticated-orcid":false,"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"9","key":"2025111311213612200_bib1","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.annonc.2024.06.016","article-title":"ESMO clinical practice guideline interim update on new targeted therapies in the first line and at relapse of chronic lymphocytic leukaemia","volume":"35","author":"Eichhorst","year":"2024","journal-title":"Ann Oncol"},{"issue":"7","key":"2025111311213612200_bib2","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S1470-2045(16)30051-1","article-title":"First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial","volume":"17","author":"Eichhorst","year":"2016","journal-title":"Lancet Oncol"},{"issue":"12","key":"2025111311213612200_bib3","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1056\/NEJMoa1313984","article-title":"Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions","volume":"370","author":"Goede","year":"2014","journal-title":"N Engl J Med"},{"issue":"1","key":"2025111311213612200_bib4","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":"12","key":"2025111311213612200_bib5","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S1470-2045(23)00452-7","article-title":"Fixed-duration ibrutinib\u2013venetoclax versus chlorambucil\u2013obinutuzumab 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":"10232","key":"2025111311213612200_bib6","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S0140-6736(20)30262-2","article-title":"Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial","volume":"395","author":"Sharman","year":"2020","journal-title":"Lancet"},{"issue":"19","key":"2025111311213612200_bib7","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":"23","key":"2025111311213612200_bib8","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1056\/NEJMoa1815281","article-title":"Venetoclax and obinutuzumab in patients with CLL and coexisting conditions","volume":"380","author":"Fischer","year":"2019","journal-title":"N Engl J Med"},{"issue":"7","key":"2025111311213612200_bib9","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.clml.2023.03.010","article-title":"Treatment discontinuation patterns for patients with chronic lymphocytic leukemia in real-world settings: results from a multi-center international study","volume":"23","author":"Shadman","year":"2023","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"1","key":"2025111311213612200_bib10","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3324\/haematol.2020.266486","article-title":"The impact of early discontinuation\/dose modification of venetoclax on outcomes in patients with relapsed\/refractory chronic lymphocytic leukemia: post-hoc analyses from the phase III MURANO study","volume":"107","author":"Mato","year":"2022","journal-title":"Haematologica"},{"issue":"6","key":"2025111311213612200_bib11","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/S1470-2045(24)00196-7","article-title":"First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA\/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial","volume":"25","author":"F\u00fcrstenau","year":"2024","journal-title":"The Lancet Oncol"},{"issue":"18","key":"2025111311213612200_bib12","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":"5.5","key":"2025111311213612200_bib13","doi-asserted-by":"crossref","first-page":"563","DOI":"10.6004\/jnccn.2023.5007","article-title":"NCCN guidelines update: chronic lymphocytic leukemia\/small lymphocytic lymphoma","volume":"21","author":"Stephens","year":"2023","journal-title":"J Natl Compr Cancer Netw"},{"key":"2025111311213612200_bib14","unstructured":"Wendtner\n              C\n            , Al-SawafO, BinderM, . Chronic Lymphocytic Leukemia (CLL). Guidelines report. Onkopedia. 2024. Accessed 17 September 2025. https:\/\/www.onkopedia.com\/de\/onkopedia\/guidelines\/chronische-lymphatische-leukaemie-cll\/@@guideline\/html\/index.html."},{"issue":"12","key":"2025111311213612200_bib15","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ajh.26367","article-title":"Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures","volume":"96","author":"Hallek","year":"2021","journal-title":"Am J Hematol"},{"key":"2025111311213612200_bib16","author":"Goede","year":"23  2017"},{"issue":"9","key":"2025111311213612200_bib17","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1038\/s41375-021-01156-x","article-title":"Mapping comorbidity in chronic lymphocytic leukemia: impact of individual comorbidities on treatment, mortality, and causes of death","volume":"35","author":"Rotbain","year":"2021","journal-title":"Leukemia"},{"issue":"5","key":"2025111311213612200_bib18","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":"8","key":"2025111311213612200_bib19","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S1470-2045(22)00293-5","article-title":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial","volume":"23","author":"Tam","year":"2022","journal-title":"Lancet Oncol"},{"issue":"1","key":"2025111311213612200_bib20","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Shimabukuro-Vornhagen","year":"2018","journal-title":"J Immunother Cancer"},{"issue":"3","key":"2025111311213612200_bib21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/cncr.31790","article-title":"The role of neuro-immune interactions in cancer-related fatigue: biobehavioral risk factors and mechanisms","volume":"125","author":"Bower","year":"2019","journal-title":"Cancer"},{"issue":"10","key":"2025111311213612200_bib22","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrclinonc.2014.127","article-title":"Cancer-related fatigue--mechanisms, risk factors, and treatments","volume":"11","author":"Bower","year":"2014","journal-title":"Nat Rev Clin Oncol"},{"issue":"1","key":"2025111311213612200_bib23","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1182\/hematology.2020000120","article-title":"Preventing and monitoring for tumor lysis syndrome and other toxicities of venetoclax during treatment of chronic lymphocytic leukemia","volume":"2020","author":"Fischer","year":"2020","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"4","key":"2025111311213612200_bib24","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3109\/10428194.2015.1091933","article-title":"Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL Study Group","volume":"57","author":"Goede","year":"2016","journal-title":"Leuk Lymphoma"},{"issue":"13","key":"2025111311213612200_bib25","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1182\/blood.2023020195","article-title":"Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL","volume":"142","author":"van der Straten","year":"2023","journal-title":"Blood"},{"issue":"19","key":"2025111311213612200_bib26","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1182\/blood-2016-12-737346","article-title":"Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL\/SLL","volume":"129","author":"Barr","year":"2017","journal-title":"Blood"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2025028899\/2420027\/blood_bld-2025-028899-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2025028899\/2420027\/blood_bld-2025-028899-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T16:21:44Z","timestamp":1763050904000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/146\/20\/2406\/546906\/The-impact-of-fitness-and-dose-intensity-on"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":26,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2025,11,13]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2025028899","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11,13]]},"published":{"date-parts":[[2025,11,13]]}}}