Abstract
Simple SummaryChronic myeloid leukemia (CML) is a blood cancer. Unlike other cancers CML treatment is lifelong and many patients experience side effects. For those patients who respond well to treatment and achieve deep molecular remission, quality of life is impacted because of continuous treatment. In this review, we look at emerging clinical trials which aim to investigate which patients can safely stop treatment. Treatment-free remission is the ultimate goal for CML patients, but there is still a gap in our knowledge as to why some patients can achieve treatment-free remission, while others relapse when treatment is stopped. Here we discuss if there are any prognostic factors that can predict the best candidates who qualify for treatment discontinuation, with a view to keeping them in remission.Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKI became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40–60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon retreatment, indicating TKI discontinuation is safe. However, there is still a gap in understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it examines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.
Highlights
Chronic myeloid leukaemia (CML) is a heterogeneous haematopoietic disorder and is considered the first model in cancer for targeted therapy [1]
BCR–ABL1 became a therapeutic target for leukaemic cells and paved the way for the development of tyrosine kinase inhibitors (TKI) that dramatically improved the survival of CML patients [8,9]
A sub-study to the EURO-SKI trial held by the Nordic CML study group (NCMLSG) reported that patients with high rates of mature (CD57+) and cytotoxic (CD16+ and CD57+) natural killer (NK) cells at the time of TKI discontinuation have higher possibility of successful treatment-free remission (TFR) [93] and this suggests the importance of the surveillance of baseline immune markers before TKI discontinuation
Summary
Chronic myeloid leukaemia (CML) is a heterogeneous haematopoietic disorder and is considered the first model in cancer for targeted therapy [1]. BCR–ABL1 became a therapeutic target for leukaemic cells and paved the way for the development of tyrosine kinase inhibitors (TKI) that dramatically improved the survival of CML patients [8,9]. Patients on TKI, achieve deep molecular response (DMR) which improves the survival rates and reduces the chance of disease progression in the future [15,16,17]. This review aims to discuss the concept, mechanism, and trials of treatment-free remission (TFR) and reviews potential predictors of the success or the failure of TFR. It aims to show how far the concept of TFR can be clinically applicable
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