Molecular remission after tyrosine kinase inhibitor cessation in chronic myeloid leukemia (CML): A systematic review and meta-analysis.

Abstract

e18601 Background: Tyrosine kinase inhibitors (TKIs) have transformed the management of chronic myeloid leukemia (CML), enabling many patients to achieve deep molecular responses. Discontinuation of TKIs with the goal of treatment-free remission (TFR) is now an important therapeutic consideration, but relapse rates remain variable across studies. Methods: We systematically searched PubMed, Embase, and Scopus from inception to August 31, 2025, for prospective and observational studies reporting TFR outcomes in adults with chronic-phase CML following TKI cessation. Proportions of patients in TFR at 6, 12, 24, and 36 months were pooled using random-effects meta-analysis. Heterogeneity was assessed with the I² statistic. Risk of bias was evaluated with the Newcastle–Ottawa Scale (NOS), and certainty of evidence was graded using GRADE. Meta-regression was performed to examine the association between TKI duration and TFR outcomes. The review protocol was registered on PROSPERO (CRD420251143733). Results: Sixteen studies comprising 2,156 patients were included. The pooled TFR rates were 60% (95% CI, 54–65%) at 6 months, 55% (95% CI, 49–60%) at 12 months, 54% (95% CI, 48–59%) at 24 months, and 52% (95% CI, 45–59%) at 36 months, with substantial heterogeneity (I² >80%). Most relapses occurred within the first 12 months. Meta-regression showed a positive association between longer TKI duration and higher 6-month TFR rates (TFR6mo = 0.0835 + 0.2744×log10[median TKI duration, months]). The certainty of evidence for all outcomes was rated as moderate. Conclusions: Approximately half of patients with chronic-phase CML who discontinue TKI therapy sustain long-term TFR. Longer TKI exposure is associated with improved success, supporting guideline recommendations to ensure durable deep molecular remission before discontinuation. These findings reinforce the feasibility of TFR as a treatment goal while highlighting the importance of careful patient selection and close monitoring.