Activated Memory Cytotoxic T-Lymphocytes and T-Cell Receptor Vβ Clonality Predict Treatment-Free Remission After Tyrosine Kinase Inhibitor Discontinuation in Chronic-Phase Chronic Myeloid Leukemia: A 1-Year Prospective Immuno-Monitoring Study

We prospectively evaluated whether cytotoxic T-lymphocyte (CTL) activation and T-cell receptor (TCR) Vβ clonality predict treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) cessation in chronic-phase chronic myeloid leukemia (CML). Forty-five patients with sustained deep molecular response (DMR) were enrolled (On-TKI, <i>n</i> = 38; Off-TKI, <i>n</i> = 7) and underwent one-year immuno-monitoring from consent. The primary endpoint was 12-month TFR, defined as retention of MR4. Overall, 32/45 patients (71%) maintained TFR at 12 months. Longer TKI exposure and stable DMR were associated with TFR; notably, patients fulfilling "≥7 years of TKI plus ≥1 year of DMR" and exhibiting CTL activation features-CD8 > CD4, memory > effector, and/or highly activated CTL clones on TCR Vβ repertoire-showed the highest likelihood of durable TFR. By contrast, NK cells, effector Tregs, and G-/M-MDSCs did not discriminate TFR status in this cohort. Although antigen specificity against CML stem cells was not directly tested, the memory-dominant CTL phenotype is consistent with immune control after antigen reduction. These findings suggest that a simple, clinically accessible strategy based on flow cytometric CTL profiling and TCR Vβ clonality may help inform TKI discontinuation decisions in CML. External validation is warranted to confirm transportability and refine clinical thresholds.