{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:18:03Z","timestamp":1791980283502,"version":"4.4.0"},"reference-count":13,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The frequency of patients who switch to a second\u2010line therapy from a frontline second\u2010generation (2gen) tyrosine kinase inhibitor (TKI) such as dasatinib and nilotinib, is still substantially unknown. We retrospectively investigated a large series of chronic phase chronic myeloid leukemia (CP\u2010CML) patients initially treated with 2gen TKIs monitored through the Italian Medicines Agency (AIFA Agenzia Italiana del farmaco) registries. Overall, 2420 patients were analyzed over a period of 6\u00a0years. One hundred and fifty\u2010seven patients (16.3%) treated with dasatinib and 164 treated with nilotinib (11.3%) have switched to another drug, with an overall frequency of 13.2%. In the dasatinib cohort, 39.4% of patients changed treatment for failure and 36.3% for intolerance as compared to 45.7% and 27.4% respectively in the nilotinib cohort. Overall, the median time to switch due to resistance was 293\u00a0days, whereas it was 317\u00a0days in case of intolerance. Resistance was observed mainly in younger male patients with high\u2010risk features, while intolerance was not related to any baseline parameter. After resistance\/intolerance to nilotinib, the majority of patients switched to dasatinib (53.8%) whereas in case of frontline dasatinib to ponatinib (43.2%). To the best of our knowledge these data provide the first report on the frequency of discontinuation of frontline 2gen TKIs and on the main causes and pattern of choice to a second\u2010line therapy in the real\u2010life setting.<\/jats:p>","DOI":"10.1002\/cam4.3071","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T09:39:04Z","timestamp":1587548344000},"page":"4160-4165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["How many chronic myeloid leukemia patients who started a frontline second\u2010generation tyrosine kinase inhibitor have to switch to a second\u2010line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA)"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-6162","authenticated-orcid":false,"given":"Massimo","family":"Breccia","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine Az. Policlinico Umberto I\u2010Sapienza University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7934-9034","authenticated-orcid":false,"given":"Pier Paolo","family":"Olimpieri","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odoardo","family":"Olimpieri","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Pane","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Napoli Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0812","authenticated-orcid":false,"given":"Alessandra","family":"Iurlo","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Foggi","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Cirilli","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Colatrella","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Gozzo","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Summa","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Corradini","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano &amp; Divisione Ematologia Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Russo","sequence":"additional","affiliation":[{"name":"Italian Medicines Agency Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the AIFA\u2019s Monitoring Registries Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.8154"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.38"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609324"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8899"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2013.02.025"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V63.4.789.789"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2015.03.006"},{"key":"e_1_2_8_10_1","first-page":"11","article-title":"Long\u2010term molecular and cytogenetic response and survival outcomes with imatinib 400 mg, imatinib 800 mg, dasatinib, and nilotinib in patients with chronic\u2010phase chronic myeloid leukemia: retrospective analysis of patient data from five clinical trials","volume":"2","author":"Jain P","year":"2015","journal-title":"Lancet Hematol"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24887"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2019.025"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.440"},{"key":"e_1_2_8_14_1","first-page":"e299","article-title":"Imatinib\u2010treated chronic myeloid leukemia patients with discordant response between cytogenetic and molecular tests at 3 and 6 month time\u2010points have a reduced probability of subsequent optimal response","volume":"100","author":"Bonifacio M","year":"2015","journal-title":"Haematologica"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.3071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.3071","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T10:45:29Z","timestamp":1692787529000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.3071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,22]]},"references-count":13,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/cam4.3071"],"URL":"https:\/\/doi.org\/10.1002\/cam4.3071","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,22]]},"assertion":[{"value":"2020-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}