6-month IS value predicts MR4.5 attainment and TKI discontinuation eligibility in CML patientsTrial Shows Early Markers Predict Success in Chronic Myeloid Leukemia

Among patients with chronic myeloid leukemia (CML) aiming for tyrosine kinase inhibitor (TKI) discontinuation, second-generation TKIs (2G-TKIs) are used as one of the first-line therapy options because they induce faster and deeper molecular responses (MR) than imatinib. However, predictors of attaining and sustaining MR4.5 (BCR::ABL1 International Scale [IS] ≤0.0032%) during 2G-TKI therapy remain undefined. We analyzed 431 patients enrolled in the phase 3 Japan Adult Leukemia Study Group CML212 trial comparing nilotinib at 300 mg twice daily (n = 218) and dasatinib at 100 mg once daily (n = 213) as first-line therapy. The objective was to identify predictors of MR4.5 attainment and TKI discontinuation eligibility (TDE). Candidate variables assessed within 6 months included the European Treatment and Outcome Study (EUTOS) Long-Term Survival (ELTS) score; BCR::ABL1 IS at baseline, 3 months, and 6 months; and IS-derived halving times (HT), HT (0-3) and HT (3-6). TDE was defined as ≥3 years of TKI therapy with ≥2 consecutive years of sustained MR4.5. With a median follow-up of 3.0 years, the cumulative incidence of MR4.5 was 46.6%, and 36.3% of patients achieving MR4.5 met TDE criteria. In multivariable models, HT (0-3) (subdistribution hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.09-4.55) and the 6-month IS value (HR, 0.38; 95% CI, 0.31-0.47) were independent predictors of MR4.5 attainment, whereas only the 6-month IS value predicted TDE (odds ratio, 0.37; 95% CI, 0.24-0.56). This study demonstrates that MR at 6 months after TKI initiation has important clinical value in early stratification of MR4.5 attainment and TDE in patients receiving 2G-TKI therapy.