Are the currently prescribed doses of tyrosine kinase inhibitors too high for elderly patients with chronic myeloid leukemia?

This study investigated the prescribed doses of tyrosine kinase inhibitors (TKIs) and the outcomes of elderly patients with chronic myeloid leukemia (CML). The study concluded that the currently prescribed TKI dose might be higher than necessary in elderly patients.

TKIs such as imatinib (Glivec), dasatinib (Sprycel), nilotinib (Tasigna), and radotinib (Supect) are target therapy drugs for leukemia. The recommended doses of TKIs for the chronic-phase CML phase are – imatinib 400 mg/day, dasatinib 100 mg/day, nilotinib 600 mg/day, and radotinib 600 mg/day. TKIs can improve patients’ survival at the chronic phase of CML. However, TKIs cause more complications in elderly patients compared to younger ones.

Human organs become less responsive to drugs with age. Therefore, TKIs do not work effectively in old patients and often cause negative side effects. As a result, physicians need to reduce TKI dose or stop treatment in elderly patients. This in turn negatively affects their survival. Although, it is unknown if the current recommended TKI dose is adequate or too high for these patients.

This study included 378 patients with CML aged 70 and older. All patients were prescribed TKIs between 2005-2013. Among them, 85.7% received imatinib, 29.1% received dasatinib, 24.6% received nilotinib, and  4% received radotinib. Patients were followed up for 53 months on average.

In 12.2% of patients, the initial dose was lower than the recommended dose for chronic-phase CML. 65.9% of patients were receiving reduced TKI doses at the last follow-up. The 5-year overall survival (OS) probability was estimated to be 61.0%. The 10-years OS probability was estimated to be 24.9%. 

This study concluded that the current recommended TKI doses might be too high for elderly patients with CML. It also suggested that a lower TKI dose did not affect the survival of these patients. 

This study looked back in time to analyze patients’ data and calculate survival probability. It also lacked information on why the TKI doses were reduced in the elderly patients. More real-time studies that directly test TKI doses in elderly CML patients are needed.