Tyrosine kinase inhibitor therapy in chronic myeloid leukemia: update on key adverse events

Abstract

Current treatment recommendations for chronic myeloid leukemia (CML) are guided by results from multiple clinical trials involving tyrosine kinase inhibitors that target BCR-ABL1. Consideration of the unique clinical benefits and potential risks associated with each tyrosine kinase inhibitor approved for the treatment of CML is crucial for physicians when recommending the most appropriate therapy for each patient. Monitoring for and prompt management of adverse events may increase adherence to therapy and optimize patient outcomes. Here we provide an overview of the efficacy and safety of tyrosine kinase inhibitors approved for the treatment of CML, as well as recommendations for the management of key adverse events reported with these agents in clinical trials involving patients with CML.

Keywords:

• adverse events
• bosutinib
• chronic myeloid leukemia
• dasatinib
• imatinib
• nilotinib
• ponatinib
• safety
• tolerability
• tyrosine kinase inhibitors

Financial & competing interests disclosure

F Giles has received research support from Novartis and Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical editorial assistance was utilized in the production of this manuscript and performed by Staci Heise, PhD, Nicole Parker, PhD, Jonathan Morgan, PhD of Articulate Science and funded by Novartis Pharmaceuticals.

Key issues

• Several tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 are approved for the treatment of patients with chronic myeloid leukemia (CML).

• More than 10 years of data from prospective clinical trials have demonstrated that TKIs are effective and well tolerated in patients with CML.

• Long-term monitoring for response and any adverse events (AEs) occurring in patients on TKIs is essential for maintaining uninterrupted therapy and reducing the risk of disease progression.

• Understanding the tolerability profiles and AEs that may potentially occur on TKI therapy may help physicians in suggesting an appropriate TKI for their patients.

• Each of the approved TKIs (imatinib, nilotinib, dasatinib, bosutinib and ponatinib) is associated with a different tolerability profile.

• Preclinical studies have explored the kinase inhibition properties of TKIs and potential mechanisms that may be involved in processes such as myelosuppression, cardiac toxicity and fluid retention. However, the precise mechanisms underlying these AEs remain poorly understood.

• Chronic low-grade AEs occurring with TKIs can reduce patient quality of life and lead to reduced adherence.

• In addition to selection of an appropriate TKI, monitoring for AEs and proper management of any events is essential in helping patients with CML achieve a life expectancy and quality of life that are comparable to that of the general population.