{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:26:17Z","timestamp":1784204777120,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Since the advent of imatinib, more potent next-generation tyrosine kinase inhibitors (TKIs) and asciminib have expanded therapeutic options for chronic myeloid leukemia (CML). Treatment-free remission (TFR) is an important goal in CML management, but only ~30% of patients can achieve it, leaving many on lifelong therapy. TKIs are usually used in escalating order of potency, but in patients ineligible for or failing TFR, \u201cdowngrading\u201d to safer, lower-potency agents may be advantageous. Methods: We analyzed this strategy in 157 patients across 29 Italian CML Campus centres. Data were collected via e-forms in July 2024. Prognostic scores at diagnosis did not influence downgrading. Results: The most downgraded TKIs were nilotinib (47%) and dasatinib (37%). Imatinib was the most frequent target agent (69.7%), followed by nilotinib and bosutinib. The majority underwent downgrading during first-line therapy and most after prior dose de-escalation. Adverse events were the leading reason for downgrading (79%). Notably, in 52.6% of cases, molecular responses improved afterwards. Twenty-one patients subsequently attempted TFR, with 17 (81%) remaining treatment-free at a median follow-up of 22 months. Conclusions: These results show that, beyond the known role of de-escalation, downgrading represents a new, feasible approach to maintaining long-term control, limiting toxicity and costs, and favouring TFR.<\/jats:p>","DOI":"10.3390\/cancers18101656","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T12:30:51Z","timestamp":1779280251000},"page":"1656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Transitioning from High-Potency to Low-Potency Inhibitors in Chronic Myeloid Leukemia (CML) Patients: The Downgrading-Impact (D-IMPACT) Project"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6491","authenticated-orcid":false,"given":"Elisabetta","family":"Abruzzese","sequence":"first","affiliation":[{"name":"Department of Hematology, S. Eugenio Hospital, Tor Vergata University, ASL Roma 2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Crugnola","sequence":"additional","affiliation":[{"name":"Hematology Unit and BMT, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1661-2065","authenticated-orcid":false,"given":"Luca","family":"Garuffo","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplant Unit, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-5676","authenticated-orcid":false,"given":"Uros","family":"Markovic","sequence":"additional","affiliation":[{"name":"Hematology and Bone Marrow Transplatation Unit, Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3393-6334","authenticated-orcid":false,"given":"Malgorzata Monika","family":"Trawinska","sequence":"additional","affiliation":[{"name":"Department of Hematology, S. Eugenio Hospital, Tor Vergata University, ASL Roma 2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Barulli","sequence":"additional","affiliation":[{"name":"Divisione di Ematologia di Muraglia, CTMO Ospedale San Salvatore, 61121 Pesaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Maggi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, Ospedale S.G. Moscati, 74010 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Hematology, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-023X","authenticated-orcid":false,"given":"Daniele","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3743-2693","authenticated-orcid":false,"given":"Daniele","family":"Sannipoli","sequence":"additional","affiliation":[{"name":"San Raffaele Scientific Institute\u2014IRCCS, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3432-3373","authenticated-orcid":false,"given":"Mariella","family":"D\u2019Adda","sequence":"additional","affiliation":[{"name":"S.C. Ematologia, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Chiara","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, 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 Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella Vita","family":"Russo Rossi","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, \u201cAldo Moro\u201d University School of Medicine, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Beltrami","sequence":"additional","affiliation":[{"name":"U.O. 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