Abstract
The treatment of chronic myeloid leukemia (CML) has been radically changed by the approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity. CML is now managed as a chronic disease requiring long-term treatment and close molecular monitoring. It has been shown that in a substantial number of patients who have achieved a stable deep molecular response (DMR), TKI treatment can be safely discontinued without loss of response. Therefore, treatment-free remission (TFR), through the achievement of a DMR, is increasingly regarded as a feasible treatment goal in many CML patients. However, only nilotinib has approval in this setting and a number of controversial aspects remain regarding treatment choices and timings, predictive factors, patient communication, and optimal strategies to achieve successful TFR. This narrative review aims to provide a comprehensive overview on how to optimize the path to DMR and TFR in patients with CML, and discusses recent data and future directions.
Highlights
The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment [1]
Univariate analysis identified the speed of molecular relapse after the first TKI discontinuation attempt as being the only factor significantly associated with outcome during the second attempt; the treatment-free remission (TFR) probability at 24 months was significantly higher in patients who remained in deep molecular response (DMR) at 3 months after the first attempt to discontinue TKI compared with those who lost major molecular response (MMR) within 3 months (72 vs. 36%)
The number and potency of available treatments for CML patients have significantly increased in recent years, making therapeutic decisions more complex and treatment goals more ambitious
Summary
The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment [1]. Five TKIs are approved for the treatment of CML: imatinib, the first TKI approved for this indication; second-generation TKIs, nilotinib, dasatinib, and bosutinib; and ponatinib, a third-generation TKI [2,3,4,5,6]. Nilotinib, and dasatinib are currently recommended for both first- and second-line treatments, bosutinib and ponatinib for second and. The European LeukemiaNet (ELN) and European Society for Medical Oncology (ESMO) guidelines recommend basing the choice of first-line TKI on treatment goal, age and comorbidities, considering the safety profile of the TKI [7, 8]. Distinct safety profiles for each of imatinib, nilotinib, and dasatinib have emerged from clinical trials and clinical practice [9, 12,13,14]
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