Treatment Free Remission (TFR) in Chronic Phase‐Chronic Myeloid Leukemia (CP‐CML): Analysis of Predictive Factors and Novel Baseline Scoring System to Predict Molecular Relapse

ABSTRACT Background Treatment free remission (TFR) is a key treatment goal in chronic‐phase chronic myeloid leukemia (CP‐CML) patients with sustained deep molecular response (DMR). While clinical trials report that approximately 40%–50% of such patients can discontinue tyrosine kinase inhibitors (TKIs) without presenting a molecular relapse (MRec), real‐world data remain limited. Optimizing patient selection before TKI discontinuation is crucial for CML management and resource allocation. Methods We conducted a single‐center retrospective study on CP‐CML patients who discontinued TKIs to evaluate the rate and duration of successful TFR and to identify factors predictive of MRec. Eligibility required prior TKI treatment ≥ 3 years, a minimum molecular response (MR) of MR4.0 before discontinuation, and subsequent serial MR monitoring. MRec was defined as the loss of major MR (MMR). Results Of the 118 consecutive CP‐CML patients, 60.2% were on imatinib and 39.8% on 2G‐TKIs before attempting TFR. Median TKI treatment duration was 10.6 years, and median stable DMR duration was 6.1 years. After a median follow‐up of 72.5 months, 34 patients (28.8%) had an MRec, and estimated MRec‐free survival was 79.7% at 6 months and 69.9% overall. Multivariate analysis identified three factors associated with shorter TFR: High‐risk Sokal score (HR 2.93, p = 0.018), stable DMR duration before TKI suspension < 5 years (HR 3.63, p = 0.002), and prior unstable DMR (HR 2.47, p = 0.019). The BASE‐TFR score, assigning one point per factor, stratified patients into low‐risk, intermediate‐risk (HR 4.19, p = 0.009) and high‐risk (HR 14.06, p < 0.001) for MRec. Conclusions TFR is feasible in real‐world settings. BASE‐TFR score may help to better identify candidates for TKI discontinuation in real‐life settings.