Atrial fibrillation in CLL patients on ibrutinib
Prof Florence Cymbalista – University of Paris, Paris, France
I belong to the French Co-operative Group which is now called the French Innovative Leukaemia Organisation, FILO. I came here for the meeting and I presented, in fact, two presentations that were related to work that had been done in the group. So the first presentation was more a technical one because in France we assess MRD, minimal residual disease, in CLL in a multi-centric setting. So it was very important for us to have a very sensitive MRD but to have it in a harmonised way in all our centres. So that’s why I presented all the steps of harmonisation that we have been through to have an eight colour cytometry test for MRD that works in the same way in all our centres and that is very sensitive because we go below 106. So that was the topic of the first presentation, which was very technical but it’s interesting because we have a common trial with the Australian group and that kind of harmonisation allows to work across the oceans between two co-operative groups that are thousands of kilometres apart and that can do the same thing.
The other topic was you know that we are using more and more of these novel Bcr inhibitors. We have been using quite a lot of ibrutinib; we have heard quite a lot about ibrutinib in that meeting but all we have heard was within trials. In France we had an early access programme for ibrutinib and during that programme any physician, any haematologist, could ask for ibrutinib for the patient. So we had kind of a rush and 600 patients were treated. We had the impression when we discussed that AFib, atrial fibrillation, was probably seen more often than what was described in the trials. So we decided to have a survey amongst ten centres who had prescribed enough ibrutinib over ten patients. We found by that that we had a frequency that was close to a little over 10% of onset of atrial fibrillation and, as opposed to what was said in the trials, all the patients needed to be treated, all the patients received anti-arrhythmic therapy and, whether it was a good idea or not, ibrutinib was discontinued in more than 40% of the patients. So it was not without consequences. So the presentation here was about these 23 patients I presented and we didn’t find any real risk factors, these patients didn’t have episodes of AFib before, only three patients had. The only trigger that we found was that five patients had a recent infection but otherwise we didn’t find any specific risk factor. So the message is more it was an advocacy for guidelines. We need to involve cardiologists; we need to have systematic halter and we really need to work on these atrial fibrillations because they are manageable. But even if they are manageable we have to study them more and have guidelines on how to treat them and guidelines on what to do – are we going to leave them on ibrutinib which is probably possible but we also have to be careful with the treatment. Like, for example, amiodarone which is the most used anti-arrhythmic is a mild inhibitor of CIP which is the pathway that uses ibrutinib and, for example with amiodarone it might be necessary to lower a little bit the dose of ibrutinib. So all these things need guidelines and that was the reason of the presentation today.
