Cancer Treatment Today

Under the updated guideline from the National Comprehensive Cancer Network (NCCN) for the management of chronic myeloid leukemia (CML), discontinuation of TKI therapy is considered safe with careful monitoring in adult patients with CML in the chronic phase who achieve and maintain a major molecular response (MMR).1

Supporting evidence for this guideline update were presented Neil P. Shah, MD, PhD, at the 2019 NCCN Annual Conference, showing that about half of patients who attempt to discontinue their TKI after maintenance of MMR remain in treatment-free remission after 5 years..

Among the criteria required for successful discontinuation of TKI therapy is achievement and maintenance of 4 log reduction in BCR-ABL transcripts (MR4) for at least 2 years. But, here this parameter is not the one to be monitored.

Across TKI discontinuation trials, treatment-free remission rates after maintaining deep molecular responseusing various definitionsfor at least 1 year ranged from 40% to 60%.3 Bearing these studies in mind, there has been a desire to make TKI discontinuation available to a larger number of patients.
With relaxing the threshold for stopping treatment with TKIs, the threshold at which resuming therapy should be liberalized as well, he added, to loss of a 3-log reduction, as stated in the current guideline.

In patients who relapsed after stopping TKI treatment a first time, a second TKI discontinuation may be successful in those who regained deep molecular response following TKI rechallenge.4

Shah NP. NCCN guidelines updates: discontinuing TKI therapy in the treatment of chronic myeloid leukemia. Presented at 2019 NCCN Annual Conference; March 21-23, 2019; Orlando, FL.

Etienne G, Guilhot J, Rea D, et al. Long-term follow-up of the French Stop Imatinib (STIM1) study in patients with chronic myeloid leukemia. J Clin Oncol. 2017;35(3):298-305. doi: 10.1200/JCO.2016.68.2914.

Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747-757. doi: 10.1016/S1470-2045(18)30192-X.

Legros L, Nicolini FE, Etienne G, et al. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer. 2017;123(22):4403-4410. doi: 10.1002/cncr.30885.

Mahon FX, Etienne G. Deep molecular response in chronic myeloid leukemia: the new goal of therapy? Clin Cancer Res. 2014;20(2):310-322. doi: 10.1158/1078-0432.CCR-13-1988.