EHA 2015

Are CML patients being treated to the correct standard?

Dr Verena Hoffmann - Ludwig Maximilian University, Munich, Germany

It’s a marvellous thing that these tyrosine kinase inhibitors, imatinib specifically, have transformed the scene in chronic myeloid leukaemia. You were looking what happens in a population. Now, why were you choosing to study that rather than clinical studies?

Because the clinical studies always have in them exclusion criteria which select patients out of the population. There are other diseases where you can see it’s very specific which patients are selected for clinical trials. So the results of the clinical trials are not necessarily applicable for all the patients who are out there and do not meet the criteria of the study.

Tell me, would you, about your study. What did you do?

We put up a European population-based registry. So in 20 countries we had… in the bigger countries we’d choose regions, so we predefined where we would register all the patients and then we tried to really register every newly diagnosed patients with Ph positive CML and register their demographic data and baseline data and also follow them up for treatment and outcome.

And how many patients did you look at and what did you find?

Almost 3,000. So the population we were looking at were over 19 million and 2,904 of them diseased of CML. What we found was that actually the population of clinical trials is pretty exactly the population we see in the population-based registry. So the patients are not very selected in the clinical trials. The only thing is that a lot of clinical trials only choose patients in chronic phase.

What kind of survival rates were you getting in the real world, as compared with the clinical studies?

I’m actually not really making the difference between real world because there are a lot of patients in the clinical trials. So that is real world too, those are also CML patients. What we see is pretty similar survival rates and also progression free survival rates, so 98% overall survival after 12 months and 95% after 24 months. So that is pretty similar for what we see in clinical trials.

What is this telling clinicians, then, about therapy for CML?

Therapy is working well. We also registered the kind of treatments patients receive. So most of them receive imatinib according to the ELN guidelines, so I think that is very good to see that the TKI treatments reach a lot of patients. We also hope that even more patients will receive TKIs after the patent runs out. So we see a lot of confirming the ELN recommendations in the patients.

What did you find out about toxicities, though?

We did not register, we did not collect, toxicities themselves. We did collect treatment switches according… or we divided up for the reason for treatment failure and for side effects. There were patients, a lot of patients, switching treatments also for side effects. About 25% were switched out of their first line treatment and those were split up in treatment failure and side effects.

And adherence to therapy is an issue, you were talking about this here at the European Haematology Association. Is it safe to stop taking some of these TKIs because they do seem to have a lasting effect, don’t they?

Yes, they do. There are a lot of clinical trials going on now which are studying what happens if you stop TKI, what kind of response do you need to have had if you want to stop. But it’s not a final result there so I would not recommend just stopping TKIs outside of clinical trials and after close interaction with your doctor.

It seems, basically, you’ve got quite a lot of reassurance about the fact that therapy works. What do you advise clinicians to make of all of this, if you could summarise?

Prescribe TKIs. I’m a statistician so I’m not a clinician myself but overall you see that especially the imatinib treatment is working very well. It does not have as many side effects as the second generation TKIs have, or it’s at least better studied, so we really are glad about that. There is a lot of studying going on now of second generation TKIs and of stopping treatment in patients that do very well with their treatment. So keep on looking at what the studies say but in general the guidelines are good and we are working on just approving those.