Adverse Events Associated with ATP-Competitive BCR-ABL1 Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

Abstract

Long-term survival without transformation to blast phase CML has become a reality in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 oncoprotein. However, the majority of patients need to be treated during their entire lifespan; thus outcome does not solely depend on treatment efficacy but also on how well therapy is tolerated. Although TKIs have shown an overall favorable efficacy versus toxicity balance, many patients may encounter drug-related adverse events. These usually occur early after treatment initiation, are mild to moderate in intensity and resolve spontaneously, or are easily controlled with adequate supportive care, TKI dose reduction, or switch to an alternative TKI. However, evidence has emerged that second- and third- generation TKIs may sometimes threaten vital organs such as the cardiovascular system, the lung, and the liver, especially when comorbidities are present. Thus the decision regarding which TKI should be used and at what dose must take into account CML-related, TKI-related, and patient-related variables. The purpose of this chapter is to provide an up-to-date review of common adverse events associated with TKIs and how these events may be managed.