Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia

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 >= 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: 75-96). 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 < 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 >= 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: 1.8-206.2), 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: 0.63-0.81), 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.