Stopping treatment following response in CML

This article reviewed the safety of stopping tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia patients who have responded to treatment. This review concluded that TKI therapy can lead to a functional cure, and retreatment is possible if the disease recurs.

TKI therapy, such as imatinib (Gleevac), is the standard treatment option for chronic myeloid leukemia (CML). TKIs block a protein involved in cancer cell growth and spread. TKI therapy has improved life expectancy in CML patients to levels close to the general population. However, this type of therapy must be used indefinitely.

Patients who achieve a deep molecular response (DMR; a decrease or disappearance of BCR-ABL, an abnormal gene responsible for CML) have low risk of disease progression. Several studies have suggested that it may be safe for these patients to end TKI therapy. 

This review examined the safety and effectiveness of stopping TKI therapy in patients who have achieved DMR.

One study included 100 patients who had been treated with imatinib. These patients had undetectable levels of BCR-ABL for 2 years before stopping treatment. After an average of 60 months, 38% were molecular response free (no detectable BCR-ABL). Of the 61 recurrences, 95% occurred in the first 7 months after treatment ended.

A second study included 80 patients. A molecular recurrence (return of BCR-ABL) occurred in 36%. Most occurred in the first 6 months after treatment ended.

In a study of patients who stopped treatment with other TKI therapies (dasatinib or nilotinib), 61.4% were recurrence free at 12 months. A second study included 63 patients who stopped dasatinib treatment. 52.3% experienced a recurrence within 7 months. All regained a DMR within 6 months of restarting treatment (most within 3 months).

A large study of 868 patients reported that 62% retained molecular response at 6 months, and 51% at 24 months. 80% of patients who restarted treatment regained molecular response. 

This review concluded that TKI therapy has led to a functional cure of CML. Stopping therapy can lead to recurrences, but the disease remains responsive to treatment. 

TKI therapy leads to a functional cure, but leukemia cells still remain in the body, and relapses could occur. Some believe, therefore, that treatment discontinuation is still very experimental, and should only occur as part of clinical trials.