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Review
. 2018 Apr 10:9:43-50.
doi: 10.2147/JBM.S129821. eCollection 2018.

Bosutinib in chronic myeloid leukemia: patient selection and perspectives

Susanne Isfort  1   2 , Tim H Brümmendorf  1
Affiliations
Review

Bosutinib in chronic myeloid leukemia: patient selection and perspectives

Susanne Isfort et al. J Blood Med. .

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.

Keywords: individual comorbidity profile; side effect profile; tyrosine kinase inhibitors.

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Conflict of interest statement

Disclosure SI received Honoraria (Advisory boards, lectures) from BMS, Novartis, Pfizer, Ariad (meanwhile Incyte) and travel grants from Roche, Mundipharma, Amgen, Hexal, Pfizer and Novartis. THB serves on the Adisory boards of Novartis, Pfizer, Ariad (now Incyte) and provides research support for Novartis and Pfizer. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study 200: Patient cohorts (n=570) in second+ line. Notes: Data from Cortes et al. #indicates bosutinib is not indicated for Ph+ ALL; *indicates primary efficacy endpoint of the study was the MCyR rate at week 24 in patients with imatinib-resistant CP CML previously treated with only one prior TKI (imatinib); **indicates three chronic phase CML patients in fourth-line, and one nilotinib intolerant patient in third-line treatment. Abbreviations: ALL, acute lymphocytic leukemia; AP, accelerated phase; BP, blastic phase; CML, chronic myeloid leukemia; CP, chronic phase; MCyR, major cytogenetic response.
Figure 2
Figure 2
Recommendations for TKI treatment with regard to comorbidity status. Note: Adapted with permission from Wolf D, Brümmendorf TH, Isfort S. Individualisierte Therapie der CML: Bedeutung patienten- und krankheitsspezifischer Parameter für eine optimale Therapiewahl. [Individualized therapy for CML: importance of patient- and illness- specific parameters in order to choose the optimal therapy]. Thieme Praxis Report. 2015;7:9.
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