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NAOS, a real-world study, complements these trials with real-world (rw) acalabrutinib data generated from clinical practice.\u00a0This retrospective, non-interventional, longitudinal study was conducted in 59 sites in France in adult patients initiating acalabrutinib for CLL in 2021\u20132022.The study assessed rw use (time to discontinuation, TTD) and effectiveness (rw progression free survival, rwPFS) in first line (L1) and relapsed\/refractory setting (L2+). At the time of the analysis, data were collected from routine medical records since the treatment start up to the end of 2022. Of the 485 enrolled patients, 58.8% were in L1 and 41.2% in L2+. Median age was 73 (L1) and 77 (L2+) years. Of them, 55.1% had a prior cardiovascular history, 25.1% del(17p)\/<jats:italic>TP53<\/jats:italic>m, and 67.4% were u<jats:italic>IGHV<\/jats:italic>. Among 188 patients initiated in 2021 (119 L1; 69 L2+), 31.4% discontinued treatment, 14.9% of whom due to adverse event (AE). The 12-month rwPFS rate was 93.1% (88.5\u201397.7) in L1 and 87% (79.0-94.9) in L2\u2009+\u2009patients with no significant difference based on del17p\/<jats:italic>TP53<\/jats:italic>m (<jats:italic>p<\/jats:italic>\u2009=\u20090.21) and on <jats:italic>IGHV<\/jats:italic> status (<jats:italic>p<\/jats:italic>\u2009=\u20090.34). AEs leading to treatment changes occurred in 40 patients (21.3%), grade 3\/4 AE in 9.6%, while cardiac disorders occurred in only 2.1% of patients.\u00a0NAOS, one of the largest real-world cohorts of acalabrutinib-treated CLL patients in Europe, showed effectiveness and safety consistent with clinical trials, despite an older population with more cardiovascular comorbidities.<\/jats:p>","DOI":"10.1007\/s00277-025-06498-5","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:29:49Z","timestamp":1753864189000},"page":"4175-4187","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Real-world efficacy and safety outcomes of acalabrutinib in chronic lymphocytic leukemia: primary results of a French multicentre observational study (NAOS)"],"prefix":"10.1007","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3666-3442","authenticated-orcid":false,"given":"Anne","family":"Quinquenel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Lepr\u00eatre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Sarah","family":"Dilhuydy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Bussot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zora","family":"Marjanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Benbrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Gui\u00e8ze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Santagostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dartigeas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Feugier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Roos-Weil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghandi","family":"Damaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Laribi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loic","family":"Ysebaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"issue":"1","key":"6498_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.annonc.2020.09.019","volume":"32","author":"B Eichhorst","year":"2021","unstructured":"Eichhorst B, Robak T, Montserrat E et al (2021) Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. 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SL has declared consultancy fees with AstraZeneca, Janssen Cilag, Abbvie, Beigene and Lilly. MSD has declared consultancy fees with Abbvie, Janssen-Cilag, AstraZeneca and Beigene. LB has has declared consultancy fees with Janssen Cilag, AstraZeneca, Beigene and Abbvie. RG has declared consultancy fees with Janssen Cilag, AstraZeneca, Beigene, Roche, Abbvie and Lilly. CD has declared board, consultation with Beigene, Janssen, Lilly, Abbvie, et AstraZeneca, local meeting with Beigene, Janssen; travel congress with: Beigene, Lilly, Janssen, Abbvie, AstraZeneca; travel grant and congress: Beigene, Lilly, Janssen, Abbvie, AstraZeneca. PF has declared consultancy fees with AstraZeneca, Janssen Cilag, Abbvie, Beigene and Lilly. DRW declared consultancy fees with AstraZeneca, Janssen Cilag, Abbvie, Beigene and Lilly. KL has grants from AstraZeneca and Abbvie, board of directors with Takeda, Novartis, Abbvie, Beigene, Pfizer, Jansen Cilag, honoraria with Jansen Cilag, BMS, GSK, Takeda, AbbVie, Amgen. LY has declared consultancy fees with Abbvie AstraZeneca Beigene BMS Gilead Janssen Cilag and Roche. VL has declared consultancy fees with Abbvie, AstraZeneca, BeiGene, Janssen-Cilag, Lilly. Other authors (ZM, OB, AS, GD) declared no COI.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Patients were informed of the study and did not oppose to their data collection before being enrolled, with adapted measures regarding deceased patients in accordance with local regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}