{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:18:12Z","timestamp":1783937892616,"version":"3.55.0"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second\u2010generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65\u00a0years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real\u2010world practice. The cohort was characterized by advanced age (median 78.1\u00a0years, range 65.1\u201394.5), with over half of the patients presenting with Binet stage C disease. Two\u2010thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow\u2010up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56\u20130.73,\n p<\/jats:italic>\n \u00a0<\u00a00.001). At 12\u00a0months, the discontinuation rate was significantly higher among patients with a CFS >\u00a03 (29.2%) compared with those with a CFS \u2264\u00a03 (8.8%) (\n p<\/jats:italic>\n \u00a0<\u00a00.001); among conventional prognostic variables, only relapsed\/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease\u2010related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.\n <\/jats:p>","DOI":"10.1002\/hon.70166","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T17:35:38Z","timestamp":1767029738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Frailty Scale as a Predictor of Early Treatment Discontinuation in Elderly Patients With Chronic Lymphocytic Leukemia Treated With Zanubrutinib: A Multicenter Real\u2010World Study"],"prefix":"10.1002","volume":"44","author":[{"given":"Ernesto","family":"Vigna","sequence":"first","affiliation":[{"name":"Department of Onco\u2010Hematology Hematology Unit Azienda Ospedaliera Annunziata Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica Antonia","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Onco\u2010Hematology Hematology Unit Azienda Ospedaliera Annunziata Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Pitino","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC\u2010CNR) Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Pasquale","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) SOC Clinica Ematologia Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isacco","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Department of Engineering for Innovation Medicine University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7393-1138","authenticated-orcid":false,"given":"Riccardo","family":"Moia","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Translational Medicine Universit\u00e0 del Piemonte Orientale Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Visentin","sequence":"additional","affiliation":[{"name":"Hematology Unit Department of Medicine\u2010DIMED University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-381X","authenticated-orcid":false,"given":"Alessandro","family":"Sanna","sequence":"additional","affiliation":[{"name":"Hematology Unit Deparment of Oncology AOU\u2010Careggi Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Motta","sequence":"additional","affiliation":[{"name":"Department of Hematology ASST Spedali Civili di Brescia Lombardia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Moratti","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) SOC Clinica Ematologia Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-9862","authenticated-orcid":false,"given":"Paolo","family":"Sportoletti","sequence":"additional","affiliation":[{"name":"Centro di Ricerca Emato\u2010Oncologica (CREO) Dipartimento di Medicina e Chirurgia Universit\u00e0 di Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Chiarenza","sequence":"additional","affiliation":[{"name":"Division of Hematology Azienda Policlinico\u2010S. 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