EHA 2016

Results from the EURO-SKI cessation trial of TKIs in CML

Dr Johan Richter - Lund University, Lund, Sweden

I’ve been presenting the EURO-SKI trial, Euro Stop Tyrosine Kinase Inhibitors in CML. So this is a large European study about stopping TKI therapy in patients with a good response to those drugs in chronic myeloid leukaemia. So it’s a study with more than 800 patients so I think it will be the largest cessation trial ever done.

Can you tell us what the impact of stopping TKI inhibitors has on patients?

I think it has various impacts on various patients. Of course if you are a patient to have had side effects to the drugs stopping the drug will be a way of getting away from those side effects. Also instead of going on lifelong medication this could, in an ideal world, be a limited time that you have to take the drug for chronic myeloid leukaemia.

When it comes to disease response what are the impacts there?

There are requirements for stopping and I would like to underline those and that is that you really need to know the disease, the transcript, the BCR-ABL transcript type is something that is required to know before you do the stopping because that is what you monitor after having stopped the therapy. You monitor that by PCR and in the case of there is a molecular recurrence of the disease you have to start therapy again. All in all, looking at all the stopping trials that are performed, about half of the patients do need to reinitiate therapy so far, that is from 40-60% in all trials performed, also the recent ones that have been published now lately at both ASCO and EHA.

And from the EURO-SKI trial in particular, how many patients are doing well with cessation?

The primary endpoint of the study was at six months, so that’s 62% being in molecular relapse free survival. If you then follow them for a bit longer to twelve months it’s 56% and if then projected at three years, which is the duration of the study, it’s about 50% of the patients. This is in a setting, it’s more decentralised and a bit more liberal inclusion criteria than most cessation trials that have been performed previously.

You mentioned some of the patient outcomes in terms of avoiding the side effects earlier, are there any other related outcomes that come with cessation of therapy?

You mentioned side effects and then there is this thing that we actually discovered or we saw first in EURO-SKI is that also stopping a drug might give rise to side effects. So we have this TKI withdrawal syndrome with symptoms from the musculoskeletal system. In most patients it’s transient but about a third, almost a third, of the patients stopping TKI get some symptoms from doing so. Of course this is a bit confusing since also TKI treatment in general, like imatinib but also the other TKIs, can give rise to musculoskeletal pain or cramps and so on. So we don’t really know the background for this TKI withdrawal syndrome yet but it’s something that needs to be looked into.

Are there any trials that would be following that up that that you could name?

Hopefully we will be able to do some more analysis of the EURO-SKI trial to see if this correlates to duration of therapy, if it correlates to your ability to stop etc.

That answers all the questions I have prepared, is there anything else that you would like to add to maybe summarise the trial?

We now are at a stage in terms of TKI stopping where we have had a number of trials that have been published this year and we need to take the data from these trials and hopefully merge them into some sensible guidelines so we can, on that basis, move this slowly and orderly into the ordinary everyday clinic.