preheader BJH 1

header website

Cessation of tyrosine kinase inhibitor treatment in chronic myeloid leukemia patients with deep molecular response: results of the EURO-SKI trial

In one of the largest ever trials to assess the safety of stopping tyrosine kinase inhibitor (TKI) therapy, about half of 821 chronic myeloid leukemia (CML) patients showed no evidence of relapse two years after treatment cessation. These data suggest that some patients can safely discontinue TKI use.

TKIs have dramatically improved survival in CML patients, with a high proportion of patients reaching deep molecular responses (DMR). The effectiveness of stopping TKI treatment is a key question regarding the management of CML. In several studies, it has been proven that a substantial part of patients in DMR can safely and successfully stop TKI therapy. However, the exact preconditions for stopping CML treatments are not yet defined.

The EURO-SKI trial included 821 chronic phase CML patients without prior TKI failure, who were treated with imatinib, nilotinib or dasatinib. All participants had a stable, extremely low level of detectable leukemia markers (BCR-ABL <0.01% on the international scale, MR4) for at least one year before TKI cessation. In this study, a molecular recurrence (MR) was defined as the loss of the major molecular response (MMR, BCR-ABL <0.1% IS) at any one point.

In total, 750 patients had evaluable molecular data for the estimation of the molecular recurrence free survival (MRFS). Of these patients, 348 lost MMR and 5 died in remission. The MRFS rate was 62% at 6 months, 56% at 12 months and 52% two years after stopping the TKI therapy. Of the patients who experienced leukemia recurrence, most regained their previous remission level after resuming TKI therapy and no study participants progressed to a dangerous state of advanced disease. Study participants who had taken a TKI for more than 5.8 years before stopping were significantly less likely to experience a relapse within the first six months (relapse occurred in 34.5% of these patients) compared to those who had been on the therapy for a shorter duration (57.4%). Each additional year of TKI therapy increased a patient’s chances of successful TKI discontinuation by about 16 percent.

In summary, stopping TKI therapy in a very large cohort of CML-patients appeared feasible and safe, with high MRFS rates being achieved. A longer duration of imatinib-therapy (optimal ≥ 5.8 years) prior to stopping TKI therapy was also shown to be associated with a higher probability of MRFS.


Mahon F-X, Richte J, Guilhot J, et al. Cessation of Tyrosine Kinase Inhibitors Treatment in Chronic Myeloid Leukemia Patients with Deep Molecular Response: Results of the Euro-Ski Trial. Presented at ASH 2016; Abstract 787.

Speaker François-Xavier Mahon


François-Xavier Mahon, MD, PhD,
Insitut Bergonié, university of Bordeaux, Bordeaux, France


See: Keyslides


Back to Top