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The story of tyrosine kinase inhibitors discontinuation in clinical practice

Abstract Chronic myeloid leukemia is the first example of successful clinical use of tyrosine kinase inhibitors (TKIs). Blockade of oncogenic BCR-ABL1 tyrosine kinase activity by imatinib translated into an impressive demonstration of clinical and biological control of the disease. Historically, the primary objective of TKIs use was to achieve long-term survival. Today this is a reality for the majority of patients. The rapid development of BCR-ABL1 quantification by RT-qPCR has facilitated the monitoring of residual disease. Molecular response has emerged as a new therapeutic objective, opening the door to TKIs discontinuation. The first prospective stop study in patients in deep molecular response was initiated in 2004, with today nearly 15 years of follow-up. The pioneering observations of this study followed by numerous stop-studies have led to a new therapeutic goal of treatment-free remission. Five cases of patients who discontinued TKIs are reviewed, illustrating the current issues and challenges surrounding this approach.