Clinical and biological predictors of treatment-free remission in CML.

Chronic Myeloid Leukemia (CML) is characterized by the Philadelphia chromosome t(9:22) and results in the BCR::ABL1 fusion gene. Since the evolution of targeted therapy in the form of tyrosine kinase inhibitors (TKIs), overall survival has improved to 94% at 5 years. Early studies identified that approximately half of patients could maintain a major molecular remission (MMR), i.e. BCR::ABL1 ≤ 0.1%, in the absence of TKI therapy. This is termed treatment-free remission (TFR). Identifying clinical and biological predictors of TFR has become a major goal in CML. In this review, we discuss clinical predictors of TFR, including features at diagnosis, molecular response and kinetics, depth and duration of molecular response, and dose reduction prior to TKI cessation in determining TFR success. We also discuss advances in highly sensitive Minimal Residual Disease (MRD) assays, consider the genomic profile of CML patients and review the role of the immune environment in sustaining TFR.