ASH 2013 - New Orleans, LA, US
Chronic lymphocytic leukaemia: A new treatment era is born
Dr John Gribben - Barts Cancer Institute, London, UK
There’s a great deal of excitement about CLL at the moment with the number of new drugs which are in development and which are showing such incredible promise in this disease. The educational session this morning covered three broad topics. Professor Hallek from Cologne, who is the chair of the German CLL study group, presented an overview of how we treat patients with CLL currently and how we can start to think about how many of these more novel agents are going to be incorporated into how we treat patients in the future. He set out the rationale for the way that they’re providing the backbone, how they’ve always done a series of studies comparing treatment A with treatment A plus B to look whether B adds anything and presented to us little snapshots of information we’re going to be hearing at the ASH meeting itself from particularly the CLL11 and the CLL10 study. Now, the CLL11 study was a study which is quite important because it focussed on more elderly, more frail patients with CLL and of course that forms the majority of our patients with that disease. Exciting there because most studies have excluded that patient population even though they’re the majority of patients. That study is going to be presented in full at the plenary session at ASH but Professor Hallek gave us the highlights, demonstrating that the addition of the new antibody obinutuzumab in combination with chlorambucil was very much more effective than chlorambucil alone.
He gave us a flavour of what results are going to be presented on Monday from the CLL10 study which, again, was a German CLL study group led study which compared FCR, our current standard of therapy, with BR, bendamustine in combination with rituximab. This was designed as what we call a non-inferiority study, that is it was not believed that BR would be better than FCR but that it was hoped that it would be much less toxic. The results of the study showed that yes it was less toxic and was very well tolerated by some of the older patients but it does look as if, from the results of that study, that FCR is a better therapy than BR.
He then followed that up with thinking about all the novel agents which are out there which look so exciting and particularly ibrutinib, idelalisib and ABT199, which are all at various stages of development in CLL. How exciting that data is and how we can start to think about do we add those in to chemotherapy or might we be on the threshold of starting what we call a chemo-free way of treating CLL by using those drugs. You’ve got questions then relating to the challenge of how we think about adding these agents which we know are going to be extremely expensive into this patient population and how we might afford it.
I then talked about the role of allogeneic stem cell transplant in CLL. Allogeneic stem cell transplant using cells from a donor is the only approach we have right now which can cure CLL. It’s unfortunately not applicable to the vast majority of patients with CLL who are too frail and elderly to be able to withstand that type of approach. But what I used from that was if we can start to think about how a patient’s own immune system can attack the cancer, can we look at ways in which we could get someone’s own immune system to do that? So I talked about the way that CLL cells suppress patients’ own immune systems, ways we’re looking at to repair that, and in particular I talked about some recent data using these so-called CAR cells or chimeric antigen receptor cells, where a gene for a receptor is put into the T-cells, patients’ own T-cells, which then recognises the CLL cells. From the studies being performed at the University of Pennsylvania in Philadelphia, some very exciting data there suggesting we can switch on patients own cells to do this.
Lastly, Tait Shanafelt from the Mayo Clinic looked at the issue of how do we define fitness for chemotherapy with CLL. What are the factors we should think about and how do we decide what’s the right treatment for the right patient. Clearly you want to be able to offer your patients the most, and our patients want, the most effective therapy but we’ve got to balance that against the toxicity. The toxicity of these therapies is very much higher usually in patients who already have other diseases – heart disease, renal disease, those sorts of factors. What Dr Shanafelt did was took us through the current thinking about how is the right way to think about tailoring therapy. What comes out from that is that chronological age is not the factor that should be used. You can be 65, you can be very fit and you can tolerate therapy extremely well; you can be 75, be extremely fit and tolerate even aggressive chemotherapy well but you also could be quite frail and not able to tolerate that therapy. And we’re looking for more objective tools than just your doctor making that assessment of this looking at you walking in. I think that’s very important because we are seeing therapies now which are extremely effective in patients and we’re withholding that therapy because we don’t think the patient would tolerate it. We really want to be doing that on very solid ground and Dr Shanafelt took us through the process of where we’ve got to. There’s a workshop which is being set up by the International Workshop for CLL looking at that factor and we’re trying to design a tool, which will be used in clinical trials in the first instance but eventually used in clinical practice in doctors’ offices, that can be used to assess whether or not a patient is able to tolerate more aggressive chemotherapies or not.
