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.
- 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.