Treatment Free Remission (TFR) in Chronic Phase-Chronic Myeloid Leukemia (CP-CML): Analysis of Predictive Factors and...

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.

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).

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.

TFR is feasible in real-world settings. BASE-TFR score may help to better identify candidates for TKI discontinuation in real-life settings.