THE ITALIAN MULTICENTRIC RANDOMIZED OPTKIMA TRIAL ON FIXED VS PROGRESSIVE INTERMITTENT TKI THERAPY IN CML ELDERLY PATIENTS: 3-YEARS OF MOLECULAR RESPONSE AND QUALITY OF LIFE MONITORING AFTER COMPLETING THE TREATMENT PLAN.

- Both FIXED and PROGRESSIVE intermittent tyrosine kinase inhibitor therapy are feasible and safe schedules in elderly patients with sustained major or deep molecular response. - The PROGRESSIVE intermittent schedule is associated with a higher incidence of molecular remission 3.0 loss. - The Health-Related Quality of Life improved during both intermittent schedules. - The PROGRESSIVE schedule was considered by Clinicians as a valid tool to select patients eligible for tyrosine kinase inhibitor discontinuation. Background: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment. Materials and Methods: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR) 3.0 and to improve Health -Related Quality of Life (HRQoL) in CML elderly patients. Results: A total of 215 patients in stable MR 3.0 /MR 4.0 were randomized to receive an intermittent TKI schedule 1 month ON -1 month OFF for 3 years (FIXED arm; n = 111) vs. a progressive de-escalation TKI dose up to one-third of the starting dose at the 3rd year (PROGRESSIVE arm; n = 104). Two hundred three patients completed the 3rd year of OPTkIMA study. At the last follow-up, MR 3.0 loss was 27% vs. 46% ( P = .005) in the FIXED vs PROGRESSIVE arm, respectively. None of these patients experienced disease progression. The 3 -year probability of maintaining the MR 3.0 was 59% vs. 53%, respectively ( P = .13). HRQoL globally improved from the baseline to the 3rd year, without any significant difference between the 2 arms. After the 3rd year, the proportion of patients who was address to TKI discontinuation in the 2 arms was 36% (FIXED) vs. 58% (PROGRESSIVE) ( P = .03). Conclusions: The intensification of intermittent TKI therapy is associated with a higher incidence of MR 3.0 loss, but those patients who maintain the MR 3.0 molecular response at the end of the study have been frequently considered eligible for TFR. The HRQoL generally improved during the de-escalation therapy in both randomization arms.