Evaluating blood vessel-related side effects of long-term use of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia.

This study examined the association between long-term use of three different tyrosine kinase inhibitors (TKIs) and the occurrence of vascular (blood vessel) adverse events (side effects; VAEs) in patients with chronic myeloid leukemia (CML). The data showed a possibly higher risk of developing VAEs when patients with CML were treated with nilotinib and dasatinib compared to imatinib.

CML is a cancer of the bone marrow and blood that affects blood-forming cells. Abnormal changes to the BCR-ABL1 gene cause constant activation of an enzyme, tyrosine kinase (TK). As a result, cell growth becomes uncontrollable.

Nilotinib (Tasigna), dasatinib (Sprycel) and imatinib (Gleevec) are targeted therapies called TKIs, that are used in the treatment of CML. The use of TKIs has provided benefits to patients with CML but concerns exist over long-term side effects, particularly those in which blood vessels are affected. These types of side effects are known as vascular adverse events (VAEs) and may be associated with newer TKIs. However, there are some inconsistencies about this possible association between TKIs and VAEs, so further investigations are needed.

This study included 1,111 patients with CML. Patients were placed into groups based on their first-line TKI treatment. 306 patients were treated with nilotinib, 240 patients with dasatinib, and 565 patients with imatinib. The occurrence of VAEs including ischemic heart diseases (narrowing of blood vessels to the heart that leads to chest pains), stroke, cerebrovascular disease, arterial occlusive disease, and venous thromboembolism was determined. Risk factors for the development of VAEs were also explored. Patients were followed up for up to 5 years.

The most common VAEs were ischemic heart diseases. The occurrence of VAEs was highest during the first year of treatment with nilotinib and dasatinib. Potential risk factors for increased risk of VAEs were the use of nilotinib, older age, and a history of cerebrovascular diseases. Patients that used nilotinib had a significantly higher risk (by 3.13 times) of developing VAEs compared to those that used imatinib.

The risk of VAEs with nilotinib and dasatinib was higher in the first year and decreased thereafter. 

This study showed that VAEs were more common with second-generation TKIs such as dasatinib and nilotinib in the first year of treatment. The study suggested that caution should be exercised for patients with CML, using nilotinib and dasatinib as initial treatment, if older and with a history of cerebrovascular diseases.

The study was done in a Taiwanese population so results may not apply to all patients. The follow-up period was relatively short.