{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:49:36Z","timestamp":1782107376468,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"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":["Br J Haematol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Identifying chronic myeloid leukaemia (CML) patients at risk of therapeutic switch remains debated. We analysed the cumulative risk of treatment change in the CML Italian network prospective cohort based on first\u2010line tyrosine kinase inhibitors and patient characteristics. Sub\u2010hazard ratios (sHRs) were estimated using Fine and Gray multivariable models. Among 1662 patients, initial treatment consisted of imatinib for 840 (50.5%), nilotinib for 490 (29.5%) and dasatinib for 332 (20.0%). Subsequently, 492 patients (29.6%) required second\u2010line therapy, with 232 (47.1%) switching due to resistance and 176 (35.8%) due to intolerance. At 2\u2009years, the risk of resistance was 18.3% for imatinib, 8.4% for dasatinib (sHR\u2009=\u20090.32; 95% confidence interval 0.21\u20130.49) and 6.8% for nilotinib (0.29; 0.19\u20130.42). The risk of switching increased in intermediate (1.95; 1.40\u20132.72) and high Eutos long term survival (ELTS) risk (3.19; 2.10\u20134.83) but was reduced with older age (0.97 per year;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Intolerance at 2\u2009years was 8.5% for imatinib, 12.4% for dasatinib (2.55; 1.73\u20133.75) and 5.2% for nilotinib (1.04; 0.65\u20131.65). Switching to a third\u2010line therapy at 3\u2009years was 8% for imatinib, 5% for dasatinib and 4% for nilotinib. The results showed that the time to first treatment switch for resistance is shorter for younger patients, for imatinib and for intermediate\/high ELTS risks. The risk of switching for intolerance is higher for patients initially treated with dasatinib.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70332","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T01:14:13Z","timestamp":1768180453000},"page":"974-980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Risk factors and reasons for switching from front\u2010line therapy in the Italian chronic myeloid leukaemia network: A cohort study"],"prefix":"10.1111","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-6162","authenticated-orcid":false,"given":"Massimo","family":"Breccia","sequence":"first","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine Az. Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Giai","sequence":"additional","affiliation":[{"name":"Division of Hematology Azienda Ospedaliero Universitaria Citt\u00e0 Della Salute e Della Scienza di Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Rosso","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Department of Medical Sciences University of Turin  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pregno","sequence":"additional","affiliation":[{"name":"Division of Hematology Azienda Ospedaliero Universitaria Citt\u00e0 Della Salute e Della Scienza di Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Castagnetti","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Institute of Hematology \u201cL. &amp; A. Ser\u00e0gnoli\u201d  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-1686","authenticated-orcid":false,"given":"Massimiliano","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Hematology University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Capodanno","sequence":"additional","affiliation":[{"name":"Hematology AUSL Reggio Emilia  Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9449-2621","authenticated-orcid":false,"given":"Mario","family":"Tiribelli","sequence":"additional","affiliation":[{"name":"Division of Hematology and BMT Azienda Ospedaliero\u2010Universitaria di Udine  Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Stagno","sequence":"additional","affiliation":[{"name":"Hematology Section AOU Policlinico \u201cG.Martino\u201d University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Mulas","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health University of Cagliari  Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Gozzini","sequence":"additional","affiliation":[{"name":"Hematology University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Patriarca","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Universita Degli Studi del Piemonte Orientale Amedeo Avogadro  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-5298","authenticated-orcid":false,"given":"Federica","family":"Sor\u00e0","sequence":"additional","affiliation":[{"name":"Hematology and Transplant University Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Loglisci","sequence":"additional","affiliation":[{"name":"Hematology Vito Fazzi Hospital  Lecce Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella Russo","family":"Rossi","sequence":"additional","affiliation":[{"name":"Hematology University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Coppi","sequence":"additional","affiliation":[{"name":"Hematology Antonio Perrino Hospital  Brindisi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Miggiano","sequence":"additional","affiliation":[{"name":"Ospedale S. 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