EHA 17

New drugs on the CML horizon; choosing the correct therapies

Jan Geissler – Co-founder of CML Advocates Network
Professor Giuseppe Saglio – University of Turin, Italy
Dr Delphine Rea – Saint Louis Hospital, France



JG:    Thank you very much. I’d like to come back to the topic of choice of therapy. In 2012 we have a number of approved therapies for CML, more are coming up in trials and showing encouraging results so it gets more difficult; it used to be quite easy, some years ago, where there was one major gold standard treatment that everybody got. So what are the criteria that you, as experts, would see in the choice of, on one hand, first line therapy and secondly on second line therapy?

GS:    I would say the basic principle of the therapy of CML is just to inhibit the first step. What we have to do in most cases and in most cases this is sufficient is just to inhibit the BCR-ABL tyrosine kinase activity at the highest possible level. Of course, imatinib is a quite powerful drug in doing this but we have now the results with the second generation TKI which are equally well tolerated and are producing a faster and deeper response. According to what we have seen in these trials, in the molecular analysis of this trial, they apparently define very well in a rather short time those patients who maybe will have an inferior outcome. I wouldn’t say a poor outcome because even nowadays the prognosis of the patients who do not apparently respond very well to TKI is not so bad because the risk and the overall survival is lower with respect to that of the population who is responding well but is not so low compared to other haematological malignancies, for example. Therefore, we should identify these patients because these patients are the ideal candidates maybe for association therapy that probably we will see in the next few years trying to further reduce the burden of the leukaemia in order to achieve, to expand the concept of, complete molecular response and therefore also to open the possibility to discontinue the therapy without relapse. This is what we aim for the future. Probably for some patients a good and well-tolerated TK inhibitor can be enough; for other patients we will need to add something different to obtain and to fulfil totally the achievement that we want to achieve.

JG:    This sounds very promising but, on the other hand, very complex and I know that current treatment recommendations by an expert panel in ELN has actually been published some years ago and in that time new results came up, new drugs were approved. So you’re part of that expert panel that is going to publish an updated recommendation for CML treatment, what is the expectation? How will what we’ve discussed early on influence the revision and the new treatment guidelines?

GS:    Certainly we need to be very, very practical, very simple and to establish common criteria for all the drugs that are currently available and maybe also for some drugs that will become available in the short term. I think that we will reach this goal because we will probably have very, very simple rules how to treat CML patients in different conditions. I’ve seen this morning, right this morning, that indeed a sort of scaffold for the future European LeukaemiaNet are being constructed and therefore we expect to have the publication of the next European LeukaemiaNet recommendations in 2013, in the first months of 2013.

JG:    So this is very important, I hope next year at EHA we can report about these new guidelines and recommendations.

GS:    I’m almost certain that these will be.

JG:    That’s very good. Coming to the future, as we are talking about 2013, I would be very interested – what are the most important presentations and findings that will be presented this year at EHA  here?

GS:    Would you like to start? No, I’ll start. I think that it is a prediction of the outcome of the patients which already in a very early time point looking at the dynamics of the response. There are several reports with several TK inhibitors and I would say that all have very, very similar data. This, of course, is something which makes our decisions, it’s also the basis for the European LeukaemiaNet recommendation, easier because we will have rather clear, not very clear but clear data, on which we could base our decision.

DR:    Yes, and also the update about this large randomised trial that compared imatinib to second generation tyrosine kinase inhibitors, we know that the very early results were highly promising and the drugs had their registration in the front line setting due to these very early results. But still it is very important to see that year after year these excellent initial results are maintained in time. This is also a very crucial set of data.

JG:    Thank you so much, I’m very interested to see all the presentations, I am looking forward to what we are going to hear this year at EHA. One last question I have to you is a completely different topic about adherence because that is basically an issue that is probably challenging in daily practice and has a large influence, probably, on the results we are getting in CML outcomes. I would be very interested in your perspective on adherence and how we tackle the issue.

GS:    I think that adherence is extremely important, we know it now from clear clinical data but as we can say that inhibition of BCA-ABL tyrosine kinase activity is the main step to obtain a good therapy in CML. If we do not obtain inhibition of BCA tyrosine kinase activity because we are not taking the drug, it transforms sensitive patients into resistant patients. The concept remains the same, we are not really shutting off what is really the main driver of the disease. So adherence is becoming, is a very important topic that we must explain and convey this clear message to our patients because the success of the therapy is really due to the everyday adherence to the established therapy.

DR:    Yes, of course, and adherence in fact is a major issue in all chronic diseases. CML has mostly turned into a chronic disease because the risk of transformation has become extremely low . So yes, patients have to be aware that the treatment can be efficient only if it is taken properly. But that’s not sufficient, we need to understand why there are some adherence problems in some patients and we need to help them, which means patient education, of course, and also physician education – being aware of chronic side effects, being aware of why there could be some adherence problems – can only improve the communication between the physician and the patient because the situation has to be improved on the patient’s side and also on the physician’s side. It’s only by making progress together that the situation may improve and that the adherence may remain high in the long term.

JG:    So you think that adherence, improving adherence, is not only an issue of the doctors, it is an issue of partnership between patients and doctors?

DR:    Absolutely, absolutely. This is extremely important.

GS:    Not only patients, doctors but I would say also other actors like psychologists sometimes because sometimes it’s a rather trivial phenomenon, in other cases, in most cases I would say, it’s a rather complicated phenomenon because patients sometimes are aware they’re not doing the right thing but they do it in any case and so this is what is very difficult sometimes to explain but it is what is happening. Indeed, the quality of life of the CML patients in a recent publication done by the Italian group has been shown to be better for the elderly patients, sometimes with many comorbidities, with respect to the younger population. This is because for elderly patients with maybe some other problems it’s more acceptable to add one drug and maybe to add some limitations to those already present in their life than for a younger population whose expectation in terms of quality of life are certainly higher. Therefore this, from a psychological point of view, is a very important aspect that we have to consider. And as Delphine said before, it’s true that with a chronic disease there is a problem of adherence but the consequences of poor adherence are different in different diseases because just not to be adherent to hypertension has some risk but just for the therapy of hypertension but just not to be adherent to therapy for leukaemia is a more dangerous event.

JG:    So that basically means that probably adherence is just a symptom and we need to find the cause of non-adherence and need to look at quality of life and things like that?

GS:    Absolutely.

DR:    Yes, but there is not a unique cause to poor adherence, there are maybe many causes that may differ from one patient to another.

GS:    It’s another field of investigation, I would say, because human beings are very delicate, we must take into consideration this aspect and we are dealing with something which is not trivial but has an important basis to be understood and to be solved. But it’s a rather complex phenomenon.

DR:    But we need the help of the patient in order to understand this phenomenon.

GS:    Yes, of course. I think that CML Advocates work, it’s very good work because indeed it is a sort of support for people who are not alone and they are sharing their problems, they are finding solutions and so this is a good initiative.

JG:    This is probably also the reason why the European Haematology Association this year, and the patient community, have selected quality of life – do your patients perceive quality of life the same way as you do? – as the topic of the patient advocacy session which will be covered later at this congress. I’d like to thank you so much for a very interesting discussion, Dr Rea, Dr Saglio, and I’m very much looking forward into what’s going to be presented, what we’re going to report on later on, about the new recommendations that are going to be published later on. Thank you so much.