Adverse events associated with nilotinib in chronic myeloid leukemia: mechanisms and management strategies

ABSTRACT

Introduction: Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) targeting BCR/ABL, which is used for the first-line treatment of newly diagnosed chronic myeloid leukemia (CML) patients and the second-line treatment of most CML patients who are resistant or intolerant to prior therapy that includes imatinib. In addition to common adverse reactions, long-term use of nilotinib shows some toxicities that are different from those of occurring during other BCR/ABL TKI treatments, such as cardiovascular toxicity. It is life-threatening, which would affect not only the choice of initial treatment of CML patients but also the safety of long-term medication.

Areas covered: Through searching literature and reports from PubMed and clinical trials, here we review a profile of the adverse effects induced by nilotinib. We also discuss the potential molecular toxicological mechanisms and clinical management, which may provide strategies to prevent or intervene the toxicity associated with nilotinib.

Expert opinion: Severe adverse effects associated with nilotinib limit its long-term clinical application. However, the exact mechanisms underlying these toxicities remain unclear. Future research should focus on the developing strategies to reduce the toxicities of nilotinib as well as to avoid similar toxicity in the development of new drugs.

KEYWORDS:

• Adverse events
• chronic myeloid leukemia
• management
• mechanisms
• molecular target
• nilotinib

Article highlights

• A few adverse reactions associated with nilotinib might limit the application and long-term use of nilotinib in clinics.

• Many adverse reactions of nilotinib, such as skin and subcutaneous tissue disorders, gastrointestinal disorders, musculoskeletal disorders, and general disorders are mild and can recover on their own without medical intervention. Most of the above grade 3/4 adverse events caused by nilotinib should be dealt with dose adjustment or treatment interruption.

• Although cardiovascular toxicity is uncommon among patients under nilotinib treatment, it can be life-threatening, especially for patients with high-risk factors. Patient selection together with early prevention and periodic monitoring is necessary.

• Mechanisms of adverse events associated with nilotinib are still unclear.

• Molecular mechanisms of nilotinib-associated adverse reactions are expected to be clarified in future. Therefore, the relevant biological targets can be used for prediction, diagnosis and management, so as to solve the problems of intolerance among patients with long-term use of nilotinib.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has declared advisory board and consultancy for BMS, Incyte, Novartis and Pfizer. One reviewer has declared advisory board and speaker bureau honoraria from Novartis. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82003862) and the 1022 Talent Training Program of Zhejiang Cancer Hospital.