Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid Leukemia: eligibility criteria and predictors of success

Abstract

TKI discontinuation proved to be safe and feasible in patients with CML with deep and durable molecular responses, introducing an additional treatment goal for these patients beyond overall survival. However, treatment interruption is a safe procedure only with appropriate patient selection and monitoring. Clinical and biological factors associated with better outcomes do not yet offer a precise stratification of patients according to their risk of relapse. This article aims at reviewing the leading studies present in the field in order to define eligibility criteria for discontinuation and predictors of success.

Risk of progression in chronic phase‐chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR‐PRO study

“…A large‐scale, precise quantification of the risk of CML progression after TD in the setting of TFR has not been performed. Sudden blastic transformation has also been reported as a rare event in patients in optimal molecular response who did not discontinue therapy, 24,25 suggesting that transformation may occur independently of TD 26 …”

“…Sudden blastic transformation has also been reported as a rare event in patients in optimal molecular response who did not discontinue therapy, 24,25 suggesting that transformation may occur independently of TD. 26 The main goal of the Treatment-Free Remission-PROgression (TFR-PRO) study is to obtain a precise assessment of the risk of disease progression in a cohort of CP-CML patients eligible for TD, regardless of whether they underwent a TD.…”

Caution in using second generation tyrosine kinase inhibitor, especially for first line therapy of chronic myeloid leukemia

“…Given these results and the fact that 2GEN failed to substantially decrease the risk of CML progression to accelerated phase/blast crisis, when tested against imatinib in more than 15 controlled studies in the first line setting (Table 1), 11 It is also true that 2GEN generally lead to faster decrease in minimal residual disease; however, curves come close with time, and the failure rate of treatment discontinuation after imatinib or 2GEN is not different. 12 In conclusion, the report from Bower et al highlights an important issue in the management of CML: when a normal life expectancy is the goal of the therapy, the safety of the chosen TKI becomes of paramount importance, especially for first line therapy. Further research on the incidence of second cancers and of CVD in the entire cohort of CML patients is still needed.…”

DNA Damage Response (DDR) Is Associated With Treatment-free Remission in Chronic Myeloid Leukemia Patients

“…Tyrosine kinase inhibitors (TKI) drastically improved outcome in chronic myeloid leukemia (CML): selected patients with optimal response may suspend the therapy indefinitely, after a prolonged remission. 1 However, about 50% patients relapse rapidly and must resume treatment. Relapses are likely due to residual TKI-insensitive quiescent leukemic stem cells (LSCs) that persist under TKI.…”