Safety profiles of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.

AIMS AND

OBJECTIVES

To review the use of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia (CML) and provide recommendations for managing adverse events (AEs) to maximise patient benefit.

BACKGROUND

Treatment of CML has been revolutionised with the advent of tyrosine kinase inhibitors (TKIs) that target the breakpoint cluster region-Abelson (BCR-ABL) kinase. Imatinib is the only first-line TKI currently available for the treatment of CML; however, intolerance and resistance remain significant clinical challenges. The approved second-line treatment options for CML are dasatinib, nilotinib or escalated-dose imatinib.

DESIGN

Review article.

METHODS

Searches of PubMed, ASCO and ASH electronic databases for relevant search terms were performed between July 2008-January 2009.

FINDINGS: Dasatinib has no cross-intolerance with imatinib, and the most frequent AEs (cytopenias and pleural and pericardial effusions) can generally be managed by dose interruption and reduction. Nilotinib has a high degree of haematologic cross-intolerance with first-line imatinib. As might be expected, high-dose imatinib has the potential for more severe AEs than standard-dose imatinib.

CONCLUSIONS

There are known safety issues inherent to each TKI and close monitoring by nursing staff is necessary to identify and effectively manage AEs.

RELEVANCE TO CLINICAL PRACTICE: All three TKIs have demonstrated potential for fluid retention and cardiotoxicity. Nurses should be aware of how these AEs manifest and intervene appropriately. The safety profiles of these TKIs clearly differs and it is important to consider factors such as comorbidities when making treatment decisions.