New challenges in treatment of elderly CLL patients
Prof Barbara Eichhorst- Center for Integrated Oncology, Cologne, Germany
You’ve been talking here about chronic lymphocytic leukaemia and the sort of options for older patients. I gather, however, that this is quite difficult, it isn’t easy to decide exactly what is the best option for older patients. Could you tell me what the score is right now?
That’s correct because elderly patients don’t tolerate our current standard treatment in CLL which is a relatively intense combination based on fludarabine, cyclophosphamide and rituximab. Therefore we have to decide on geriatric assessments if the patient is fit enough or not fit enough for receiving the so-called FCR regimen. There are different tools for the geriatric assessment, unfortunately in CLL there is so far no ideal tool, sometimes it’s just the impression of the doctor how the patient is coming to the doctor’s desk, sometimes it would be better if we would do more comprehensive geriatric assessments.
But the standard approach, what is that because watchful waiting is also a standard approach, isn’t it?
That’s correct. Luckily in the majority of patients they don’t need treatment immediately because, as in other indolent lymphomas, we start treating CLL when patients become symptomatic and therefore in the majority of patients watch and wait is the approach.
The standard is what now, if you do treat?
If we treat elderly patients our standard is right now to combine chlorambucil with a CD20 antibody. Right now there are three different CD20 antibodies available, one is the well-known rituximab, the other one is ofatumumab and the third one is obinutuzumab.
But you are doing some studies that hopefully will throw some light on the challenges that you face right now. Can you tell me what it is? You’ve got one in progress and another one completed so far, haven’t you?
Correct. So the CLL11 study was the study we completed already where we compared obinutuzumab plus chlorambucil versus rituximab plus chlorambucil versus chlorambucil alone showing the superiority of both antibody containing arms to chlorambucil and obinutuzumab was also better than rituximab. Also with regard to overall survival the CD20 antibodies improved the overall survival.
When you say better and improved, how much?
The improvement in the progression free survival with obinutuzumab in comparison with rituximab was 14 months, in comparison to chlorambucil alone it’s 20 months.
So there is a significant difference when you add in these targeted therapies. You’ve got a new study also coming up, the CLL14 study, what differences is that introducing?
Yes, in the CLL 14 study we address the question if we still need chemotherapy. So with all these new agents available the new approach we want to evaluate is to combine the antibody obinutuzumab with a non-chemotherapy oral agent which is in the CLL 14 study venetoclax which is not yet approved. This is a BCL2 inhibitor which drives CLL cells again into apoptosis. So we’re evaluating here a non-chemotherapy combination in the elderly patients also hoping for a good tolerability of this regimen.
And things are looking promising, to make matters more complicated you have more agents that might have specific actions, TKIs for instance.
Correct, so in CLL for one year there is the kinase inhibitor ibrutinib available as well as a PI3 kinase inhibitor, idelalisib, available. They are both approved mainly for relapsed CLL but at the upcoming ASH meeting we will also see data on ibrutinib front line therapy in the elderly patients. So maybe this data will also change the treatment of CLL patients, especially of the elderly patients that we will use these new substances more in front line therapy in the future.
What should doctors be thinking about some of these data as they come through right now for their own patients?
For their own patients with the huge amount of possibilities, at least the bigger amount of possibilities, it’s very important to discuss with the patient their needs and expectations. So to do not only a careful work-up of the disease itself, including genetic evaluation of the disease, but also looking at comorbidities, frailty of the patient, possible side effects of the medications and with all this picking up the best possible treatment option for the patient.
You’ve already established some big improvements from a more targeted approach, how far can this go? How much of an improvement can you make in the outcome of CLL in older patients?
This disease is still an incurable disease so far and, of course, therefore our approach in the elderly patients may be even cure the disease or at least achieve excellent response rates with very deep remissions meaning that the patient has the chance of not needing any relapse treatment any more during the rest of his lifespan and having the chance to die of something else than CLL. These are our aims.
So you are hoping for a functional cure?
Yes we do.
How would you sum this up for doctors, then? What’s the take home message coming out of your new evidence?
Also for the elderly patients chemoimmunotherapy approach in front line is the standard treatment and we know from several studies that administering the most effective treatment in front line therapy is the best approach. The chemotherapy backbone has to be suitable for the comorbidity burden of the patient and wherever possible include your patient into a clinical study that he may have the chance to receive one of the new drugs already in front line therapy.