Is cure for chronic myeloid leukemia possible in the tyrosine kinase inhibitors era?

The advent of tyrosine kinase inhibitors (TKI) has remarkably changed the treatment of chronic myeloid leukemia (CML). Patients treated in chronic phase can enjoy an expected survival similar to the general population. In the last few years we have found that some patients with an excellent therapeutic response can have their TKI discontinued and still remain in molecular remission.

The fact that some patients can apparently have their therapy discontinued, and stay in remission for more than 2 years, is surprising, as in-vitro work suggests the CML cell is dependent on BCR-ABL signaling and mathematical models predict that extinction of the CML stem cell reservoir will take decades of therapy. However, given that unopposed BCR-ABL causes progression and CML cells can have a rather long latency (e.g., Hiroshima survivors), it may be some time until we can be completely assured that discontinuation is without risk.

If we can safely discontinue TKI in some patients, it will have a profound effect on both the strategy and medical economics of CML therapy. A key future finding will be factor(s) that predict which patients can be discontinued without relapse, thus targeting only the patients where discontinuation will be successful.