Adverse events associated with tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia

ABSTRACT

Introduction: Tyrosine kinase inhibitors (TKIs) drastically changed the outcome of patients affected by chronic myeloid leukemia, allowing long-term improved overall survival and deep molecular responses.

Areas covered: In this review, all the related and “off target” side effects of different TKIs are reported and reviewed including their pathogenesis, and associated predisposing factors are discussed.

Expert Opinion: Appropriate identification of adverse events and classification according to CTC scale is required during therapy with TKI, considering the impact on the long-term quality of life. Specific evaluation and stratification of comorbidities and cardiovascular risk profile at baseline is suggested in order to better tailor individualized treatment strategy and identify patients who require strict monitoring of risk factors during treatment.

KEYWORDS:

• chronic myeloid leukemia
• tyrosine kinase inhibitors
• safety
• outcome

Article highlights

• Each TKI is associated to specific safety profile with non-hematologic and ‘off-target’ effects

• Imatinib, although well tolerated by the majority of patients, can be associated to mild to moderate side effects persistent over time that could affect quality of life.

• Both second-generation TKIs could affect the cardiovascular system; nilotinib has been associated to metabolic events (hyperglycemia and hypercholesterolemia) and peripheral arterial thrombotic events whereas dasatinib has been associated to pleural effusions and pulmonary arterial hypertension. Evidence of these rare events required selecting candidate at baseline according to specific comorbidity profile.

• Bosutinib has been associated to gastrointestinal side effects but with less cardiovascular events.

• Ponatinib, a third-generation TKI, required a specific level of attention regarding predisposing cardiovascular risk profile and a correct monitoring and adjustment of hypertension at each visit.

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Declaration of interest

M Breccia has received honoraria for speaking from Novartis, Bristol Meyers-Squibb, Pfizer and Ariad. 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