Introducing a prognostic score for successful treatment-free remission in chronic myeloid leukaemia

The modern management of chronic myeloid leukaemia (CML) identifies a new therapeutic goal of treatment-free remission (TFR). Half of CML patients in durable deep molecular response (DMR) (MR⁴ or better) can remain off tyrosine kinase inhibitors (TKIs) without experiencing loss of major molecular response. Despite a large number of TFR studies to date, there are no consistent predictors of successful TFR. We conducted a single-centre cohort study on 197 patients discontinuing TKIs in DMR ≥1 year and TKI therapy ≥3 years. After TKI discontinuation, 98 patients (49.7%) lost MR⁴; of these, 90 (91.8%; and 45.7% of the whole cohort) lost major molecular response (MMR or MR³) after a median of 3.8 months (1-93.3). The 2-year probability of TFR (pTFR) was 57.7%. In multivariable analysis, male sex, age at diagnosis >40 years, faster achievement of MR⁴ and longer duration of DMR were the only variables significantly associated with higher pTFR. Based on the multivariable analysis results, we built a TFR prognostic score (TPS) able to distinguish three groups with different 2-year pTFR: good (89.9%), intermediate (61.2%) and poor (18.4%) TFR probability (p < 0.0001). We validated the TPS on an independent cohort of 91 patients. We propose that the TPS could become a useful guide for CML clinicians.