Bosutinib in chronic myeloid leukemia: patient selection and perspectives

Abstract

During recent years, the therapeutic landscape in chronic myeloid leukemia (CML) has changed significantly. Since the clinical introduction of tyrosine kinase inhibitors (TKIs) approximately 15 years ago, patients’ concerns have shifted from reduced life expectancy toward long-term toxicities of TKI, depth of remission, and the probability of successful treatment discontinuation. Patients with newly diagnosed CML in chronic phase (at least with a Sokal score not exceeding intermediate) may now expect an almost normal life expectancy. However, even if almost 30% of all newly diagnosed chronic-phase patients might eventually be facing the prospect of a life without CML-specific treatment, based on current knowledge, most, if not all, patients would have to undergo an expected minimum of 5–8 years of TKI treatment and the majority would face a life-long exposure to the side-effects of TKIs. At present, 5 different TKIs are licensed for the treatment of CML, that is, imatinib, which is a first-generation TKI (including its generic derivatives); nilotinib, dasatinib, and bosutinib, which are second-generation TKIs; as well as ponatinib, which is a so-called third-generation TKI and is supposed to be used for patients harboring the T315I-mutation. One of the important, yet unanswered questions is the choice of the best possible TKI upfront for each individual patient. Bosutinib is currently licensed for patients with CML after failure or intolerance of at least 2 other TKIs. It can also be prescribed according to label if after failure of the first TKI therapy, another option does not seem feasible. This review focuses on the existing data on clinical efficacy, tolerability, and side effects of bosutinib treatment in CML patients with the aim to identify patient characteristics and treatment scenarios most suitable for treatment with bosutinib.