Discontinuing TKI therapy is possible after failed first attempt

This study examined whether treatment with tyrosine kinase inhibitors (TKIs) can be successfully discontinued after a failed first attempt in patients with chronic myeloid leukemia (CML). Researchers reported that a second TKI discontinuation attempt is safe and can be successful after a failed first attempt.

Targeted therapy is the standard first-line treatment for CML. This refers to a type of treatment that uses drugs or small molecules that block the growth and spread of cancer. Tyrosine kinase inhibitors (TKIs), such as imatinib (Gleevac), are a type of targeted therapy that block enzymes called tyrosine kinases.

About one-half of patients achieve a deep molecular response to TKI therapy (showing no more genetic abnormalities in the bone marrow). Deep molecular response is associated with a near-normal life expectancy. However, many patients lose this response once TKI therapy is stopped. Deep molecular response can be regained quickly when restarting TKI therapy. Whether a second TKI discontinuation attempt can be successful is still being investigated.

This study monitored a second TKI discontinuation attempt in 70 CML patients. Average treatment duration of first TKI therapy was 59 months. All patients lost deep molecular response after a first attempt to stop TKIs. The average time to loss of response was 5 months. Deep molecular response was regained once TKI therapy was restarted. 61 patients received the same TKI in the first and second therapy. The other 9 patients switched TKI. Imatinib was the common TKI used. Patients were followed for an average of 38.3 months after discontinuing TKI therapy for the second time.

64.3% of patients lost deep molecular response after discontinuing TKI therapy for the second time. The average time to loss of response was 5.3 months. Most relapses (54%) occurred in the first year after TKI discontinuation. None of the patients progressed to advanced-phase CML.

48% of patients were in treatment-free remission at 12 months. At 24 months, 42% of patients were in treatment-free remission. At 36 months, it was 35%.

Factors such as age, gender, risk score, TKI type, TKI duration, and molecular response duration did not affect the outcome of a second TKI discontinuation attempt. However, losing molecular response late after the first attempt appeared to reduce the risk of a molecular relapse during the second attempt. Overall, the second attempt is more successful in patients who relapse later than 3 months during a first attempt.

This study concluded that a second TKI discontinuation attempt is safe after a first failed attempt. 

Larger studies are needed to confirm the long-term safety of this strategy.