[Tyrosine kinase inhibitor therapy discontinuation for chronic myelogenous leukemia to achieve clinical cure: current status and future perspectives]

Abstract

Tyrosine kinase inhibitors (TKIs) markedly improve the prognosis of patients with chronic myelogenous leukemia (CML) by potentially helping to achieve a deep molecular response (DMR). In many clinical trials, beginning with the French Stop Imatinib (STIM1) trial, approximately 40%-60% patients with chronic CML who sustained a long DMR could discontinue TKI therapy and achieve long-term treatment-free remission (TFR). These trials have proposed many predictive factors for successful TKI therapy discontinuation, including deeper molecular response, longer duration of DMR and lack of TKI resistance prior to the discontinuation, and greater numbers of natural killer (NK) cells during the discontinuation. However, further investigations are necessary because only 20%-30% patients with chronic CML could achieve TFR. Recent studies have suggested that the recovery and reconstitution of immune effector cells against CML, including NK cells, and the elimination of CML cells using aberrant clones that are resistant to TKI are crucial for successfully achieving DMR and subsequent TFR. CML stem cells are not sensitive to TKI and could potentially interfere with TFR. Therefore, therapies targeting CML stem cells are being investigated, and the results are highly anticipated.

Keywords: CML; Discontinuation; Treatment-free remission; Tyrosine kinase inhibitors.