Abstract
The therapeutic landscape for chronic myeloid leukemia (CML) has improved significantly with the approval of tyrosine kinase inhibitors (TKIs) for therapeutic use. Most patients with optimal responses to TKIs can have a normal life expectancy. Treatment-free remission (TFR) after discontinuing TKI has increasingly become a new goal for CML treatment. However, TKI only “control“ CML, and relapse after discontinuation has become a key factor hindering patient access to attempt TFR. In this study, we reviewed studies on TKI discontinuation, including both first and second-generation TKI. We also reviewed predictors of relapse, new monitoring methods, and strategies targeting leukemic stem cells.
Highlights
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the BCR-ABL fusion gene as a result of t [9;22] (q34;q11) translocation [1]
NKG2A downregulation by dasatinib enhanced NK cell cytotoxicity and accelerated molecular responses [78]. These results demonstrated that Natural killer group 2D receptor (NKG2D) gene polymorphisms and NKG2A might serve as biomarkers for predicting Treatment-free remission (TFR) following dasatinib treatment
The results showed that tyrosine kinase inhibitors (TKIs) in combination with MDM2 inhibitor markedly induces apoptosis of Leukemic stem cells (LSCs) and enhances the efficacy of TKI by inducing pro-apoptotic and suppressing anti-apoptotic Bcl-2 proteins [138,139,140]
Summary
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the BCR-ABL fusion gene as a result of t [9;22] (q34;q11) translocation [1]. Results from multiple trials suggest that patients with a stable deep molecular response (DMR) can safely discontinue TKI without relapse, but close monitoring is recommended [13, 14]. The purpose of this review is to provide updated data on TKI discontinuation studies and analyze predictive factors, monitoring methods, and novel strategies to improve TFR. As clinical trials of TFR discontinuation show a favorable TFR rate, many patients in the real world can attempt to stop TKI to achieve TFR. In studies with longer follow-ups, the 5-year MRFS rate in the ISAV study was 47.4%, and the 8-year MRFS rate in the TWISTER study was 45% [20, 21] These results suggest that some patients can achieve a longterm safe and stable response after discontinuation of imatinib. UMRD ≥ 1.5 years; Imatinib treatment ≥2 years UMRD ≥ 2 years; Imatinib treatment ≥3 years MR4.0≥2 years; Imatinib treatment ≥3 years MR4.0 ≥ 2 years
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