{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:25:47Z","timestamp":1784917547170,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: While the outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged \u2265 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients. Methods: We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients. Results: The median age at diagnosis was 80 years (range: 75\u201396). In the first line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third line, and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In the first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e., 3-month BCR::ABL1IS &lt; 10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, respectively, with 16.6%, 35.7%, and 51.7% achieving a deep molecular response (DMR) at the same time points. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade \u2265 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (p = 0.033). Overall, the median follow-up was 46.62 months (range: 1.8\u2013206.2), and 43 patients died due to non-CML-related causes. Three patients died due to disease progression to advanced (n = 1) and blastic (n = 2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63\u20130.81), with no significant difference between the patients treated with standard doses of TKIs compared to those treated with reduced doses (p = 0.35). Conclusions: TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.<\/jats:p>","DOI":"10.3390\/jcm13010273","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T05:50:38Z","timestamp":1704261038000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safety and Efficacy of TKIs in very Elderly Patients (\u226575 Years) with Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-2936","authenticated-orcid":false,"given":"Alessandro","family":"Costa","sequence":"first","affiliation":[{"name":"1Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6491","authenticated-orcid":false,"given":"Elisabetta","family":"Abruzzese","sequence":"additional","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital, ASL Roma 2, Tor Vergata University, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-862X","authenticated-orcid":false,"given":"Roberto","family":"Latagliata","sequence":"additional","affiliation":[{"name":"Hematology Unit, Belcolle Hospital, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7487-3328","authenticated-orcid":false,"given":"Olga","family":"Mulas","sequence":"additional","affiliation":[{"name":"1Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Carmosino","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Scalzulli","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Bisegna","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ielo","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Martelli","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6585-5187","authenticated-orcid":false,"given":"Giovanni","family":"Caocci","sequence":"additional","affiliation":[{"name":"1Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-6162","authenticated-orcid":false,"given":"Massimo","family":"Breccia","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"ref_1","first-page":"49","article-title":"Staging and prognosis in chronic myelogenous leukemia","volume":"25","author":"Sokal","year":"1988","journal-title":"Semin. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1093\/jnci\/90.11.850","article-title":"A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group","volume":"90","author":"Hasford","year":"1998","journal-title":"J. Natl. 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