Five-year interim analysis of J-SKI: an observational study of TKI discontinuation in patients with CML in Japan

Treatment-free remission (TFR) is an emerging goal for patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI). However, long-term TFR durability in real-world settings remains understudied. The J-SKI study, a large observational study, was conducted to evaluate long-term TFR outcomes in Japanese patients with CML. This interim analysis included 795 eligible patients from the prospective (n = 283) and retrospective (n = 512) cohorts. With a median follow-up of 32 months (range 0.8-168) after TKI discontinuation, the 5-year TFR rate was 65.2% (95% confidence interval [CI]: 59.6-70.6%). Among patients who experienced molecular relapse, 99% (95% CI: 97-100%) regained a major molecular response after resuming TKI therapy, with no observed disease progression. Multivariate analysis identified the duration of deep molecular response (DMR) as the sole independent predictor of successful TFR, with each additional year of DMR reducing the relapse risk by 12.5% (HR: 0.875, p < 0.0001). A second TFR attempt was successful in 41% (95% CI: 22-59%) of the 32 patients. This study demonstrated that TKI discontinuation is a safe and feasible strategy in a real-world clinical setting. A sustained DMR is critical for TFR success, supporting its importance as a key therapeutic objective.