Abstract
BACKGROUND: While tyrosine kinase inhibitor (TKI) discontinuation is an established therapeutic goal, up to 60% of patients relapse after the first attempt. The feasibility of a second or third attempt at TKI discontinuation remains uncertain. Immune surveillance, particularly T-cell and natural killer (NK) cell responses, may influence treatment-free remission (TFR), although no definitive biomarkers for predicting sustained TFR have been identified. METHODS: This retrospective study included 57 chronic myeloid leukemia (CML) patients who attempted TKI discontinuation. Clinical outcomes after the first, second, and third TFR attempts were analyzed, and T cell receptor (TCR) and B-cell receptor (BCR) repertoire analyses were conducted on peripheral blood samples from 14 patients to investigate the immune landscape associated with TFR. RESULTS: TFR1 at 1 year was 67.9% (95% confidence interval [CI], 53.9%-78.4%). Sixteen patients attempted a second discontinuation, achieving a 1-year TFR2 rate of 31.2% (95% CI, 11.4%-53.6%). Patients maintaining BCR::ABL1 mRNA levels below MR(4.5) at 3 months post-TKI discontinuation had a significantly lower risk of relapse (HR, 0.099; 95% CI, 0.012-0.829; p = 0.033). TCR repertoire analysis did not reveal distinct clonal expansions of T cells; however, a significant age-related decline in T-cell diversity was observed. CONCLUSION: T-cell immunity in CML patients who have achieved a deep molecular response (DMR) may closely approximate that observed in healthy individuals.