Bosutinib for the Treatment of Philadelphia Chromosome-Positive Leukemias

Bosutinib is a dual ABL1 and SRC third generation tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with chronic myelogenous leukemia (CML) resistant to or intolerant of other BCR-ABL1 inhibitors. Bosutinib is active against leukemia cells expressing imatinib-resistant BCR-ABL1 mutations. Mechanistically, this agent may also be beneficial for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) because in preclinical animal models, SRC accelerates ALL disease development.

Here we review the current scientific and medical literature on the role of bosutinib for the treatment of CML. We address the unique therapeutic advantages of this agent, specifically its ability to inhibit mutant BCR-ABL1 kinases conferring resistance to other TKIs and its unique safety profile consisting of mainly manageable self-limited diarrhea, not cardiovascular, side effects. Long-term toxicities reported with dasatinib, nilotinib and ponatinib have not been described with bosutinib. Lastly, we present preclinical data demonstrating that bosutinib inhibits a broader range of tyrosine kinases than any other TKI, including those implicated in acute leukemia.

We propose that future studies should explore the use of bosutinib in Ph+ ALL due to its multi-kinase inhibitory activity and its relatively long-term safety compared to other second and third generation TKIs.