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With a median follow\u2010up of 42.2 months (IQR 30.8\u201354.6 months), the study involved 3306 patients with a median age of 72.1 years, of whom 42.6% had received \u22652 previous lines of treatment. The estimated 24\u2010month probabilities of being on treatment and alive were 57.9% (95% confidence interval [CI]: 59.6\u201356.2) and 76.6% (95% CI: 75.2\u201378.1), respectively. The median time to treatment discontinuation (TTD) was 31.3 months (95% CI: 29.5\u201333.5). Out of 3306 patients, 2015 (60.9%) discontinued treatment, with 993 cases attributed to death or disease progression (30.0% of all cases). Among the 1022 patients who discontinued treatment for reasons other than progression or death, 564 (17.1%) patients did so due to toxicity or medical decision, while 458 patients (13.8%) were lost to follow\u2010up. Multivariable analysis revealed that age, Eastern Cooperative Oncology Group Performance Status, the number of previous lines of therapy, refractoriness to the last treatment, and reduced renal function were associated with shorter TTD and overall survival (OS). The coexistence of 17p\u2212 and <jats:italic>TP53<\/jats:italic> mutations had an independent unfavorable impact on TTD and OS. Nonstandard doses were associated with shorter TTD and advanced stage with shorter OS. The median OS postprogression and postdiscontinuation for other reasons were estimated at 12.9 (95% CI: 11.3\u201316.2) and 22.7 months (95% CI: 20.2\u201328.3), respectively. This large real\u2010world study shows that ibrutinib is an effective treatment for R\/R CLL. Baseline patient characteristics and double\u2010hit <jats:italic>TP53<\/jats:italic> aberrations were associated with inferior prognosis, and discontinuation due to CLL progression portended a poor outcome.<\/jats:p>","DOI":"10.1002\/hem3.70017","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:37:17Z","timestamp":1728405437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Outcomes and prognostic factors in 3306 patients with relapsed\/refractory chronic lymphocytic leukemia treated with ibrutinib outside of clinical trials: A nationwide study"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8370-5190","authenticated-orcid":false,"given":"Gian Matteo","family":"Rigolin","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Paolo","family":"Olimpieri","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Summa","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Celant","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Scarf\u00f2","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele Milan Italy"},{"name":"IRCCS Ospedale San Raffaele Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pia","family":"Ballardini","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Urso","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Gambara","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cavazzini","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-7342","authenticated-orcid":false,"given":"Paolo","family":"Ghia","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele Milan Italy"},{"name":"IRCCS Ospedale San Raffaele Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cuneo","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Russo","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2020000086"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0031"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.09.019"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2856"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25638"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.147900"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.198820"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.182907"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-020-00584-3"},{"key":"e_1_2_11_11_1","unstructured":"AIFA: Italian Medicines Agency. 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