Can tyrosine kinase inhibitor treatment be stopped in CML patients with deep molecular response?

This study aimed to define the conditions necessary for stopping tyrosine kinase inhibitor treatment in patients with chronic myeloid leukemia. This study concluded that patients who maintain a deep molecular response have good molecular relapse-free survival and can be considered for treatment discontinuation.

Tyrosine kinase inhibitors (TKI) are a common treatment for patients with chronic myeloid leukemia (CML). TKIs block certain proteins involved in the growth of cancer cells. In CML, this type of treatment blocks the activity of the abnormal gene BCR-ABL1. TKIs can be discontinued (stopped) if a deep molecular response is achieved and maintained. Deep molecular response refers to no sign of BCR-ABL1, and is a sign of disease remission. However, it is not clear under what conditions treatment can be safely stopped.

This study involved 755 patients with chronic phase CML who had received TKI treatment for 3 years and had confirmed deep molecular response for minimum of 1 year. Patients were followed for an average of 27 months. 

Molecular relapse-free survival (defined by loss of major molecular response, or MMR, referring to very little BCR-ABL1 detected) was 61% at 6 months and 50% at 24 months. 49% of all patients involved lost MMR after TKI discontinuation. 1% of all patients died while in MMR for reasons unrelated to CML (heart attack, lung cancer, renal cancer and heart failure). 2% of all patients restarted TKI therapy while in MMR.

Another 1% of patients died after loss of MMR and re-initiation of TKI therapy for reasons unrelated to CML. Less than 1% of patients lost MMR even after restarting TKI therapy.

405 patients received imatinib (a TKI) as their treatment. In this group, longer treatment durations and longer deep molecular response durations were associated with increasing probability of MMR maintenance at 6 months.

This study concluded that patients with CML who have deep molecular response have good molecular relapse-free survival and should be considered for TKI discontinuation.

Consult your physician about the possibility of TKI discontinuation.