Two Year TKI Consolidation Allowed for TKI Cessation in Select Patients With CML


Research suggests some patients with CML can safely discontinue TKI therapy - NCCN guidelines published.

by Dr. C.H. Weaver M.D. 5/2019

Tyrosine kinase inhibitors (TKI) have changed the management of chronic myeloid leukemia (CML) since the discovery and development of Gleevec® (imatinib).

Patients no longer have a bone marrow transplant as their main treatment option and can survive for years taking one to several available TKI’s. Many patients however want to stop TKIs for a variety of reasons including cost, side effects, and inconvenience. Research is beginning to show that not all patients with CML require continuous TKI therapy.(1,2,3)

The STIM1 clinical study showed that patients with CML who had undetectable minimal residual disease for at least 2 years could successfully stop treatment with the TKI Gleevec, however, molecular recurrence-free survival was only 43% at 2 years. (2)

Now according to the results of the Japanese STAT2 clinical trial more than 6 in 10 CML patients remained treatment-free after successfully completing 2 years of consolidation therapy with Tasigna (nilotinib). In other words, some patients who sustain deep molecular response are able to successfully discontinue treatment with Tasigna,

The STAT2 clinical trial included 96 patients, of whom 78 sustained a deep molecular response during a 2-year consolidation phase with Tasigna 300 mg twice daily. These patients were eligible to discontinue treatment with Tasigna. Of those patients who discontinued treatment, 67.9% remained free from molecular recurrence during the first year. The estimated 3-year treatment-free survival was 62.8%.

All 29 patients who had molecular recurrence during the treatment-free phase were re-administered Tasigna. The majority (86.2%) were able to achieve rapid deep molecular response after restarting the drug, and half achieved deep molecular response within 3.5 months.

Treatment-free survival was significantly better among those patients with undetectable molecular residual disease than in patients without. The 3-year treatment-free survival was 75.6% in patients with compared with 48.6% in patients without undetectable molecular residual disease

Based on the results of the STAT2 clinical trial the researchers believe that a “TKI should be continued for more than 2 years as consolidation after achieving deep molecular response.” Individuals with CML should discuss whether discontinuing therapy as an option with their treating physician and should not ever discontinue therapy on their own.

NCCN Released Criteria for TKI Discontinuation

Patents who wish to stop their TKI after achieving and maintaining deep molecular response for at least 2 years should have access to frequent molecular monitoring, according to the guideline. Monthly molecular monitoring is recommended during the first year following discontinuation and every 6 weeks during the second year following discontinuation; and then, every 12 weeks thereafter. Patients should resume therapy with loss of major molecular response.(4)

The NCCN guidelines recommend that patients should be referred to a CML Specialty Center for at least 1 consultation to review the appropriateness of TKI discontinuation. “It is strongly encouraged to notify the NCCN panel of any potential new toxicity that may occur, or any bad [disease-related] outcome that may occur in patients who stop therapy.”


  1. Takahashi N, Nishiwaki K, Nakaselo C, et al. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan.Haematologica. 2018;103(11):1835-1842.

  2. 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;35:298-305.

  3. Takahashi N, Kyo T, Maeda Y, et al. Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia.*Haematologica.*2012;97:903-906. doi:10.3324/haematol.2011.056853.

  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.