POSTER: CML-473 Treatment-Free Remission (TFR) in Chronic-Phase Chronic Myeloid Leukemia (CP-CML): Analysis of Predictive Factors and Novel Scoring System for Molecular Recurrence

CONTEXT: TFR is the new goal for CP-CML patients with a sustained DMR. Identifying predictors of TFR success is crucial to optimize patient selection. OBJECTIVE: To evaluate the rate and duration of successful TFR after TKI discontinuation while identifying factors predicting MRec (loss of MMR). Secondary aims include analyzing time to relapse and overall safety. DESIGN: A retrospective, single-center study analyzing data of CP-CML patients who discontinued TKIs for whichever reason from 2009 to 2024. SETTING: Conducted in a specialized university hospital setting, focusing on outpatient monitoring. PATIENTS OR OTHER PARTICIPANTS: 118 consecutive CP-CML patients were included. Eligibility required prior TKI treatment ≥ 3 years, a minimum molecular response of MR4.0 (IS) before discontinuation, and serial molecular response monitoring. INTERVENTIONS: No experimental intervention; patients’ molecular response was monitored post-TKI discontinuation using RT-qPCR at predefined intervals. TKI treatment was resumed if MRec occurred. MAIN OUTCOMES MEASURES: Measurement of stable TFR rate and duration (MRec-free survival) and of MRec predictive factors. RESULTS: Eleven patients (9.3%) presented a high Sokal risk score. Most patients (60.2%) were on imatinib, while 39.8% were on 2G-TKIs. The reason to stop TKI therapy was shared-decision in 78% of cases and TKI-toxicity in 20%. Median TKI treatment duration was 10.6 years, with a median stable DMR duration before TKI discontinuation of 6.1 years. After a median follow-up of 72.5 months, 34 patients (28.8%) had an MRec. Estimated MRec-free survival was 79.7% at 6 months, 74.4% at 24 months, and 69.9% overall. Multivariate analysis identified three factors associated with a shorter TFR: high-risk Sokal score (HR 2.93, 95%CI, 1.20-7.12, p=0.018), stable DMR duration before TKI suspension < 5 years (HR 3.63, 95%CI, 1.60-8.23, p=0.002), prior unstable DMR history (HR 2.47, 95%CI, 1.16-5.23, p=0.019). A score called BASE-TFR was developed assigning one point for each of these factors, and patients were classified into low-risk (0), intermediate-risk (1) HR 4.19 (95%CI, 1.43-12.29, p=0.009) and high-risk (≥2) HR 14.06 (95%CI, 5.18-38.18, p<0.001) for MRec. CONCLUSIONS: TFR is an achievable goal in real-world settings. The BASE‑TFR score may enhance patient selection for TKI discontinuation attempts, thereby optimizing CML management and resource allocation in clinical practice. Further validation is needed to confirm these findings.