{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:36:13Z","timestamp":1793147773363,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AbbVie"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)\/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death. Venetoclax ramp-up involves gradual, stepwise increases in daily venetoclax dosing from 20 mg to 400 mg (target dose) over 5 weeks; adherence to on-label scheduling provides a tumor debulking phase, reducing the risk of TLS. The key components of safe venetoclax therapy involve assessment (radiographic evaluation and baseline blood chemistry), preparation (adequate hydration), and initiation (blood chemistry monitoring). In addition to summarizing the evidence for venetoclax\u2019s efficacy and safety, this review uses hypothetical patient scenarios based on risk level for TLS (high, medium, low) to share the authors\u2019 clinical experience with venetoclax initiation and present global approaches utilized in various treatment settings. These hypothetical scenarios highlight the importance of a multidisciplinary approach and shared decision-making, outlining best practices for venetoclax initiation and overall optimal treatment strategies in patients with CLL.<\/jats:p>","DOI":"10.3390\/cancers16050980","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T07:56:02Z","timestamp":1709106962000},"page":"980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Venetoclax Initiation in Chronic Lymphocytic Leukemia: International Insights and Innovative Approaches for Optimal Patient Care"],"prefix":"10.3390","volume":"16","author":[{"given":"Mary Ann","family":"Anderson","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, VIC 3000, Australia"},{"name":"Division of Blood Cells and Blood Cancers, The Walter and Eliza Hall Institute, Melbourne, VIC 3000, Australia"},{"name":"Peter MacCallum Cancer Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Walewska","sequence":"additional","affiliation":[{"name":"University Hospitals Dorset, NHS Foundation Trust, Bournemouth BH7 7DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidelma","family":"Hackett","sequence":"additional","affiliation":[{"name":"Cancer Services Directorate, University Hospital Limerick UL Hospitals Group, St. Nessan\u2019s Road, V94 F858 Limerick, Ireland"}],"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":"Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"Montegaard","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-6835","authenticated-orcid":false,"given":"John F.","family":"Seymour","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Haematology, Chesterfield Royal Hospital NHS Foundation Trust, Chesterfield S44 5BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Stilgenbauer","sequence":"additional","affiliation":[{"name":"Division of CLL, Department of Internal Medicine III, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Whitechurch","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2217\/fon-2020-0640","article-title":"An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia","volume":"17","author":"Salvaris","year":"2021","journal-title":"Future Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1182\/blood-2016-01-688796","article-title":"The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism","volume":"127","author":"Anderson","year":"2016","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nm.3048","article-title":"ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets","volume":"19","author":"Souers","year":"2013","journal-title":"Nat. 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