Prof Clemens Wendtner - University of Cologne, Cologne, Germany
Dr Francesc Bosch – Hospital Vall d'Hebron, Barcelona, Spain
Prof Paolo Ghia – Università Vita-Salute San Raffaele, Milan, Italy
Prof Florence Cymbalista - Hôpital Avicenne, Paris, France
CW: Hello, this is Clemens Wendtner from Amsterdam, from the CLL Current Treatment Practices meeting. Welcome to ecancer. Today I’m sitting here with three of my colleagues: Paolo Ghia from Milano, Italy, Florence Cymbalista from Paris, France and with Francesc Bosch from Barcelona, Spain. We want to discuss today some topics we have touched during the last few days. I think we have seen a revolution, or evolution at least, in the field of CLL. So what do we think, Paolo? What did we experience as changes in the treatment algorithm?
PG: Thank you, Clemens. I think that we already experienced a big change in the way we treat our patients. Indeed, last year we had three new drugs approved in Europe for the treatment of CLL patients. Those include a monoclonal antibody against CD20, the GA101, which is now approved in first line together with chlorambucil for unfit elderly patients. This was thanks to the German CLL study group and the work they have done together with an international collaboration. In addition, the new revolution is that we saw the approval of drugs which are not chemotherapeutics anymore. I'm talking about idelalisib in combination with rituximab and ibrutinib which are both so-called BCR inhibitors and they have been approved for relapsed refractory patients but, more surprisingly and very well welcome by all of us, for the first line treatment of patients with 17p deletion and p53 mutations which are the so-called high risk patients. It was definitely an unmet clinical need.
CW: So, Florence, what do you think? What are the current standards in France? Were these new drugs implemented already in the treatment algorithms, in the fit and the unfit? Where do you see a specific niche for these new drugs?
FC: I think that we are lucky in France to have these drugs available and reimbursed. So of course the first line has not changed yet because it’s still FCR for the fit patients but we are very lucky, as Paolo was saying, to have these drugs available for the 17p and p53 mutations. It’s already changing a lot for the relapsed refractory patients and we use more and more these two new drugs.
CW: What about the situation in Spain, Francesc?
FB: Yes, I think we are lucky to have the opportunity to select the particular drugs for particular patients. So it’s a new era for CLL and in Spain fortunately at the end of the year we will have all these three approved drugs for this disease.
CW: And, as discussed, we have now several options, at least two new drugs; in the field of the targeted drugs we have new antibodies available. It’s a little bit the agony of choice, I would call it. So let’s talk a little bit about the specific side effects, not only effects but side effects, of the targeted drugs. So what are your thoughts?
PG: Of course this is also a revolution from another standpoint because, as I always say, now we have to become again doctors, general practitioners. I mean that the toxicity profile of these new drugs is somehow completely different from what we have been used to in the past with chemotherapeutic regimens. So we are now facing not any more bone marrow toxicity, or at least at lower degrees, but we are facing diarrhoea or pneumonitis or atrial fibrillation as new side effects that we have to be aware of. The new drugs luckily have different toxicity profiles, somehow not completely overlapping, which help us to select the most appropriate drug based on the risk profile of our patients.
CW: So, talking about side effects, there are specific side effects of each drug. I think the French study group and French scientists are very much involved in the understanding how ibrutinib, for example, can interfere with the anticoagulation system, or the coagulation system. So what are the main messages we have heard about during this meeting and in the past few months?
FC: I think that first, as haematologists, we have to be aware that these complications should be looked for because as we were not dealing with cardiotoxic drugs before, we lose a little bit the habit of having the history, cardiac history, of the patients. Also we have a role in giving information to the general practitioners when the patients are back home because it can happen. So we need to involve the cardiologists in thinking and understanding this atrial fibrillation that happens with ibrutinib, probably in the early months but maybe also later. Also we have to be very aware of the other treatments that patients take because it seems that the influence of ibrutinib on platelet aggregation makes patients with double anti-aggregation very much at risk of bleeding. So we really need to know more and probably within the next few months we’ll probably learn more on these topics.
CW: Francesc, you have also treated many patients, I have to say, in also colitis, for example. Can you tell us a little bit more?
FB: Yes. Other drugs develop other adverse events; we are learning who is at risk to develop these adverse events, for instance colitis for idelalisib. So we are learning how to manage that, how to prevent, how to solve the problem, how to interact with other specialists Florence mentioned. So it’s a learning curve for these new toxicities we’re experiencing now.
CW: So besides side effects what are the other things we are still lacking and missing with these new drugs? What are the future perspectives we want to achieve?
PG: Of course there is a lot of enthusiasm. The efficacy of these drugs has been something that we never saw until recently. We are still not curing the patients so the future, very likely, will ask us to combine these drugs or maybe combine these drugs with the older chemotherapy in order to achieve better, more frequent complete remissions and probably even to get to a minimum residual disease status which is what we want to achieve in our patients because we know that by achieving more complete remissions and deeper complete remissions with MRD negativity status then we can also prolong the progression free survival of our patient and overall survival of our patient.
CW: The French CLL study group is doing many trials also in combination, can you report a little bit, Florence?
FC: Yes, I think that the problem is that we know nothing about the long-term right now. Right now what we think that would be interesting is try to be able to stop this treatment because until now they have been given until progression. So the idea that we had was to combine ibrutinib with GA101 and after that we try to segregate the patients. If the patients have a very good response with negativity of MRD we’ll stop the treatment but if the patients have still some disease, we’ll add some chemo to the… But the aim is to have the best response and to be able to use these drugs and stop them at some point.
FB: Yes, we have to combine more efficacy, go for better responses with minimising toxicities. So I think the new era will be to combine different drugs, maybe we will end up doing combinations but I think it is the future to combine other drugs for going for response.
FC: And you also have plans in the German group of combining?
CW: Yes. The point is that we think, at least for the fitter patients, that’s the way to move forward to also get rid more and more of the chemo part and anti-CD20 combination, even a combination of two targeted drugs. Things like this might pave a little bit the future avenue for treatment.
PG: And probably another issue that we have to explore in the next years is really also the sequence of the different drugs. Now we have these new drugs, more are coming, are now tested in phase I/phase II studies or even phase III studies. So the probability is that probably we will have many more effective drugs for our patients and then we have to understand how to combine them but also how to sequence them, which one we should be using first and which one should we use last and so on.
CW: We are just learning, I think, when a patient relapses on the one drug when you switch to the other one what can be helpful. But I agree, this is a whole treatment scenario we have to think in a more wise way also in the future.
FB: For instance, in Spain we want to start a trial combining sequentially ibrutinib followed by a monoclonal antibody in a sequential manner, hypothesising that the monoclonal antibodies are more effective after a while.
CW: There are not a lot of monoclonal antibodies. In the maintenance phase this could be also an option besides the new targeted drugs. OK, I think we have wrapped up quite a bit from the recent meeting here in Amsterdam. I hope you found this session helpful and we are all looking forward to reporting again at another opportunity. Thanks for your attention.
