Researchers Identify Risk Factors for Bosutinib-related Cardiac, Vascular Toxicities

Incidence of vascular and cardiac adverse events were low with long-term bosutinib treatment in the first-line and relapsed/refractory setting in patients with Philadelphia chromosome (Ph)-positive leukemia, including chronic myeloid leukemia, a study published in the American Journal of Hematology has shown.¹

Because vascular and cardiac safety during tyrosine kinase therapy has become an emerging issue, researchers sought to evaluate vascular and cardiac toxicities associated with long-term bosutinib treatment for Ph-positive leukemia.

For the study, researchers analyzed data from treatment-emergent adverse events and changes in Qtc intervals and ejection fraction from 2 studies: a phase 1/2 trial in relapsed/refractory Ph-positive leukemia and a phase 3 trial in treatment-naïve patients with chronic myeloid leukemia. Follow-up time was 48 months or longer for both studies.

Results showed that vascular treatment-emergent adverse events were reported in 7% of bosutinib-treated patients overall and cardiac toxicities were observed in 10%. In patients receiving first-line treatment for chronic myeloid leukemia, similar incidences of vascular and cardiac treatment-emergent adverse events were observed with bosutinib vs imatinib.

Only 4% of bosutinib-treated patients experienced grade 3 or worse vascular or cardiac events each, and no single treatment-emergent adverse event occurred in more than 2% of bosutinib-treated patients.

Researchers found that the rates of cardiac and vascular treatment-emergent adverse events were similarly low for second-line or subsequent-line bosutinib as compared with first-line bosutinib or imatinib.

The study further demonstrated performance status greater than 0 and history of vascular or cardiac disorders were prognostic of vascular and cardiac events in patients with relapsed/refractory disease. Hyperlipidemia/hypercholesterolemia and older age were prognostic of only cardiac events.

Among patients with newly diagnosed chronic myeloid leukemia, older age was prognostic of vascular and cardiac events; history of diabetes was prognostic of vascular events.

Reference

1. Cortes JE, Khoury HJ, Kantarjian H, et al. Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib [published online ahead of print April 13, 2016]. Am J Hematol. doi: 10.1002/ajh.24360.