Complexity of chronic-phase CML management after failing a second-generation TKI.

The treatment landscape of chronic myeloid leukemia (CML) was radically changed with the introduction of imatinib in 2001. With the emergence of treatment failure with imatinib, more specific and potent second- and third-generation tyrosine kinase inhibitors (TKIs) were developed. Currently, 6 TKIs and one protein synthesis inhibitor are available on the market for CML treatment. Despite the availability of these agents, it is not uncommon for some patients to experience treatment failure across several lines of therapy. Sequencing the available treatment options is a challenging task that becomes more complex after patients fail the more potent second- and third-generation TKIs. The ability to successfully salvage such patients is limited. In this paper, we will briefly review the mechanisms of treatment failure in chronic-phase CML (CP-CML) and focus on the complexity of managing patients who fail a second-generation TKI.