{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:36:10Z","timestamp":1793147770257,"version":"4.5.0"},"reference-count":40,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The treatment of chronic lymphocytic leukemia (CLL) has been transformed over the past decade based on a better understanding of disease biology, especially regarding molecular genetic drivers and relevant signaling pathways. Agents focusing on B-cell receptor (in particular Bruton tyrosine kinase [BTK]) and apoptosis (BCL2) targets have replaced chemoimmunotherapy (CIT) as the treatment standard. BTK and BCL2 inhibitor\u2212based therapy has consistently shown prolonged progression-free survival and in some instances even increased overall survival against CIT in frontline phase 3 trials. This improvement is particularly pronounced in high-risk CLL subgroups defined by unmutated IGHV, deletion 17p (17p\u2212), and\/or the mutation of TP53, making CIT in these subgroups essentially obsolete. Despite remarkable advances, these markers also retain a differential prognostic and predictive impact in the context of targeted therapies, mandating risk-stratification in frontline management. Furthermore, BTK- and BCL2-targeting agents differ in their adverse event profiles, requiring adjustment of treatment choice based on patient characteristics such as coexisting conditions, comedications, and delivery-of-care aspects.<\/jats:p>","DOI":"10.1182\/hematology.2024000656","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T10:04:36Z","timestamp":1733479476000},"page":"457-466","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":22,"title":["Risk-stratification in frontline CLL therapy: standard of care"],"prefix":"10.1182","volume":"2024","author":[{"given":"Eugen","family":"Tausch","sequence":"first","affiliation":[{"name":"Comprehensive Cancer Center Ulm and Division of CLL\u2013Internal Medicine III, Ulm University, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Schneider","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Ulm and Division of CLL\u2013Internal Medicine III, Ulm University, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Stilgenbauer","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Ulm and Division of CLL\u2013Internal Medicine III, Ulm University, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"issue":"25","key":"2024121115504951700_hem2024000656C1","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"issue":"3","key":"2024121115504951700_hem2024000656C2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.6004\/jnccn.2024.0018","article-title":"Chronic lymphocytic 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