Good morning. I’m going to present the trial entitled EURO-SKI about cessation of TKI, tyrosine kinase inhibitor, treatment in CML patients with deep molecular response. So probably you know that stopping treatment is an emerging goal of chronic myeloid leukaemia management because several studies have already demonstrated the possibility to stop treatment. We did in Lancet Oncology already six years ago, confirmed by the Austrian group, confirmed also by the French group, and recently we reported the steam study with a long follow-up which validates the concept of treatment-free remission.

So assisting deep molecular response on long-term TKI therapy seems to be necessary prior to that time to treatment free remission. However, the more precise conditions for stopping CML treatment are not yet well defined. So already four years ago we started a trial in Europe entitled EURO-SKI. The criteria for stopping treatment were less strict as compared to the previous study, in other words patients were proposed for stopping when they were in deep molecular response defined by MR4. In other words it means that the [?? 1:48] level is at 4 log reduction as compared to the beginning of the disease. This deep molecular response is sustained during one year and the patients have to be treated in three years. Every kind of TKI was possible in that study. The definition of molecular recurrence or molecular relapse in that study was loss of major molecular response. In other words, a level of [?? 2:18] more than 0.1%.

We included or we have pre-registered in that study more than 800 patients; eleven countries from Europe participated to that study. So here you have the different patients of the patient flow and disposition. The final registration was 821, because we have some screening failures and because some also exclusion and different protocol violations the analysis was performed on 758 patients. We have also proposed prognostic modelling on 448 patients only treated with imatinib de novo.

We performed an intention to stop treatment analysis among the 755 patients. Among them 373 patients lost the major molecular response. We observed four deaths and the median follow-up was around 15 months and the median follow-up for the patients who did not relapse was 26 months. As you can see on that curve, most of the events, in other words most of the loss of MMR occurred during the first six months. The probability to be off treatment still in major molecular response at 12 months is 55% and it is 50% at 24 months. So with inclusion and relapse criteria less strict than in many previous trials and with a decentralised but standardised PCR monitoring stopping of TKI therapy in a large cohort of CML patients appeared feasible and safe. This trial, closer to true life, demonstrates that half of the patients are still off treatment without molecular recurrence with a median follow-up around 15 months. The proportion of patients without recurrence, loss of MMR, after 6 months is 51% and after 18 months is 52%. Longer duration of imatinib therapy prior to TKI stop correlates with a higher probability of relapse free survival and it is really the only factor that we observed. In addition, the duration of MR4 is also significant and on Monday I will present a cut-off for the duration of MR4 because the cut-off of duration for imatinib therapy in that study was evaluated at 5.8 years. Gender, age or any other variable such as [?? 5:37] score are not able to predict the success of stopping treatment. We think that a study would be very useful and support treated new ELN recommendations.

I want to thank all of my colleagues in Europe and particularly Suzanne Saussele which is on the first floor here which is my co PI. Thank you.