Treatment-Free Remission in Chronic Myeloid Leukemia: A Systematic Review of Predictors of Successful Tyrosine Kinase Inhibitor Discontinuation

Treatment-free remission (TFR) has become an explicit therapeutic goal in chronic-phase chronic myeloid leukemia (CP-CML), yet only a minority of patients who start a tyrosine kinase inhibitor (TKI) ultimately achieve durable remission off therapy.Although several clinically relevant predictors have been identified, individual prediction of who will sustain remission remains imperfect.This systematic review was conducted to identify and synthesize original peer-reviewed studies published between 2021 and 2026 that evaluated predictors of successful TKI discontinuation in adults with CP-CML.PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published from January 1, 2021, to July 31, 2026.Primary research articles reporting molecular outcomes after TKI cessation together with an analysis of at least one candidate predictor were eligible; reviews, meta-analyses, conference abstracts, editorials, letters, protocols, and preprints were excluded.Risk of bias was appraised with the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool.Findings were synthesized narratively without meta-analysis because of heterogeneity in predictor definitions and outcome timing.Fourteen studies comprising more than 3,000 reported discontinuation attempts across Europe, North America, Asia, and Australia were included.At heterogeneous study-specific follow-up timepoints, reported TFR estimates were generally approximately 55-72%, although direct comparison was limited by differences in follow-up duration and outcome definitions; most molecular recurrences occurred within the first six months after cessation.Duration of deep molecular response (DMR) before cessation was the factor most consistently associated with TFR, supported by duration of prior TKI therapy.Residual disease below conventional detection limits, assessed by digital polymerase chain reaction (PCR) in a small number of studies, and the trajectory of BCR::ABL1 transcripts in the first three months off therapy were associated with outcome and represent promising adjunctive markers, whereas early on-treatment kinetics, transcript type, transcriptomic signatures, and immune parameters were promising but inconsistently replicated.Almost all patients regained major molecular response (MMR) after re-treatment under structured molecular monitoring, and progression was not observed.Depth and duration of molecular remission, rather than baseline prognostic scores, were most consistently associated with TFR.Prospective validation of composite molecular-immunological models is the principal research priority.