Road to treatment-free remission in chronic myeloid leukemia.

The development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) has transformed chronic myeloid leukemia into a chronic disease with near-normal life expectancy. More recently, treatment-free remission (TFR), defined as sustained molecular remission even after TKI discontinuation, has emerged as a realistic therapeutic goal and a type of functional cure. Landmark studies, including STIM1, A-STIM, EURO-SKI, ENESTfreedom, DADI, and J-SKI, have established the feasibility and safety of TFR. Their results showed that approximately half of eligible patients can successfully discontinue therapy. However, the reliable prediction of TFR success remains a major challenge. Accumulating evidence indicates that durable TFR reflects a dynamic equilibrium between residual leukemic stem cells (LSCs) and host immune surveillance. Natural killer cells and T-cell immunity contribute to maintaining remission after TKI discontinuation. Conversely, immune exhaustion and the persistence of LSCs are associated with molecular relapse. Emerging biomarkers, including immune profiling, immunogenetic markers, and minimal residual disease kinetics, may improve relapse-risk stratification. To increase the proportion of patients who achieve durable TFR, future efforts should focus on the development of risk-adapted consolidation strategies incorporating optimized TKI therapy, immune modulation, and LSC-targeted approaches.