Imatinib discontinuation in chronic myeloid leukemia patients with undetectable BCR-ABL transcript level: A systematic review and a meta-analysis

Imatinib discontinuation in chronic myeloid leukemia patients with undetectable BCR-ABL transcript level: A systematic review and a meta-analysis
Tyrosine kinase inhibitors (TKIs) have revolutionized the way in which chronic myeloid leukemia (CML) is treated, but it is unclear when - if ever - it is safe to discontinue TKIs and what the risk of relapse is after discontinuation. This study is a systematic review and meta-analysis of the literature evaluating the incidence of CML relapse following the discontinuation of TKIs in adult patients.
A literature search was performed using MEDLINE and EMBASE, and two independent reviewers performed the study selection. Studies were considered eligible if they included CML patients who discontinued TKIs, were randomized controlled trials or cohort studies and reported clinical outcomes.
15 cohort studies were included in the final analysis, encompassing 509 patients with CML, all who were treated with imatinib. Overall rate of molecular relapse of CML was 51%, with 80% of relapses occurring within the first six months following TKI discontinuation. All patients were still alive at the two year follow up and only one patient in the entire cohort progressed to a blast crisis.
Most of the trials included had only adult patients and none of the trials were RCTs. Furthermore, the confidence intervals calculated for all sub-analyses overlapped and there were a number of questions that were unable to be answered through the data gathered by this study. All patients included in the study were treated with imatinib, and there was no representation of any of the other TKIs commonly used in clinical practice.
TKIs have proven very effective in the management of CML, but questions remain regarding the duration of therapy required. This study showed that it is feasible to discontinue TKI therapy when in complete molecular remission, given that overall survival after two years was 100%, and that nearly half of patients will not relapse following discontinuation. Further study of the timing of TKI discontinuation is required.