Treatment-free Remission with First- and Second-generation Tyrosine Kinase Inhibitors

Chronic myeloid leukemia (CML) has become a chronic disease, for which the chronic phase is manageable with tyrosine kinase inhibitor (TKI) therapy. Patients with optimal responses to TKIs have achieved long-term survival, and treatment-free remission (TFR) has since become an additional treatment goal in CML. In this review, we discuss important factors to consider prior to stopping treatment. In addition, published and presented data with the first-generation TKI imatinib, as well as current clinical trials evaluating TFR with the second-generation TKIs dasatinib and nilotinib, are examined. Results obtained outside of clinical trials have been included as well. Because successful TKI discontinuation depends upon accurate BCR-ABL1 monitoring, emerging technologies are also discussed. Clinical data obtained to date indicate that for many patients who achieve deep molecular response (DMR) on TKI therapy, TFR is a safe treatment goal, and, if the response is lost, patients can expect to regain their responses immediately upon reinitiation of TKI. It is also clear that there remains much room for improvement to make TFR a successful reality for most patients. Data from ongoing trials should help refine decisions as to which patients are the best candidates to attempt TKI discontinuation with safe monitoring in place.