CLL related research from ASH 2010

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Published: 18 Feb 2011
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Dr Michael Keating- MD Anderson Cancer Center, Texas, USA
Dr Michael Keating discusses his pick of the research presented at ASH 2010. This includes trials looking at new tyrosine kinase inhibitors that target LIM-kinase, Syk, PI 3-kinase delta or BTK. Due to the low levels of toxicity, these TKIs are potentially ideal front line therapies for older cancer patients. Dr Keating talks about what we can expect from the upcoming International Workshop on CLL (IWCLL) which will be held in Texas on 28-30 October 2011.

2010 American Society of Hematology Annual Meeting 3rd - 7th December

Interview with Dr Michael Keating- MD Anderson Cancer Center, Texas, USA

CLL related research from ASH 2010

 

DS                   Dr Smith

MK                   Michael Keating

 

DS       Michael, perhaps you could just start by summarising what you think are some of the key highlights of this year’s ASH meeting in Orlando?

 

MK       I think that the meeting this year will be a very interesting one for a couple of reasons. I think that the technology to explore what’s happening with CLL is burgeoning. And we have to fit this into place, but I think that we now are aware that we have very good approaches to treatment for younger patients, and now we’re in need of more effective treatment for patients that are older.

 

We also have very good technology to measure minimal residual disease, and if that’s the goal of treatment, to get people free of Leukaemia for long periods of time, the technology is there, but I think that the major breakthrough in this year is the report on a number of small molecules that are given by mouth, that have low toxicity, that are very effective in shutting off the enzymes that are important in B-cell receptor signalling. So that there are basically, four enzyme pathways that are being looked at; one is an enzyme called Lyn Kinase, and this is being inhibited by dasatinib and bafatinib. And there’s then a CYC inhibitor which was reported in Rheumatoid Arthritis recently, in the New England Journal of Medicine. But two years ago in this meeting was found to be very active in CLL, and I’m sure either that drug or an analogue will come along, fairly soon to be explored.

 

There is an inhibitor of P83kinase Delta from Kalastoga called Kal101,which is very effective, and the updated reports are coming at this meeting. And there’s a new kid on the block called PC132765, which inhibits an enzyme Bruten’s Tyrosine Kinase. Now, Bruten was a naval physician who was looking after a child that had very severe recurrent infections, and there was no cause identified, except for a slight lowering in the Lymphocyte count. But as the technology came along, they found that he couldn’t... this child couldn’t make any gamma-globulin and as you could separate B lymphocytes from T lymphocytes, he couldn’t make any B lymphocytes.

 

So that this is a key enzyme pathway in the development of B lymphocytes, and in many cases of CLL, this enzyme is turned on, and when you give this group of drugs, within a very short period of time, all of the lymph glands tend to shrink down in one or two weeks. And they liberate the cells out into the bloodstream, so that they’re more susceptible to being killed by antibodies or just going through spontaneous cell death. So that not only do we have the clinical reports coming through, but a number of the studies that are being reported in the Biology and Basic Science programmes are explaining how this works, what we can do to make it better. And there are already studies that are being put in place for frontline treatment of older patients with these relatively non-toxic oral medications, and others that are combining these drugs with monoclonal antibodies. So I think we’re starting the second revolution.

 

DS       Very interesting, very interesting, and sort of, looking ahead, you have your next IWCLL meeting in your home town Houston, in September I believe, next year.

 

MK       Yes, late October.

 

DS       Late October, so what do you see between now and October in terms of CLL progress?

 

MK       I think that there are going to be a number of things, I think that there are maturations of some of the randomised comparative trials. I don’t think the German CLL study group comparison of FCR, which is the new standard for young, fit patients versus Bendamustine Rituximab, will be mature enough. But we certainly should be getting safety data on that comparison. And I think that we’ll have a lot more information, not only on some of these new drugs, but the understanding of the genetics is now becoming more and more precise. And I think we’ll get information on that, and the other is I think that we’re becoming more and more aware that the cure of CLL will eventually be through a mechanism of enhancing the ability of the immune system to attack CLL cells as they’re being born.

 

I think the other area that will occur will be some of the exploratory studies with Chlorambusil plus or minus Rituxan, to look at whether Rituximab should be approved for frontline in older patients. I think we’ll have some more information on Ofatumumab and its activities. I think that the more mature results of stem cell transplants will be made available as well, so that I think that this is a time of incredible... incredibly rapid movement in the CLL area. Now we just have to put all these things in place, but I’m hopeful that many of these new agents will be approved relatively quickly, because they are so effective and so well-tolerated.

 

DS       So from a patient’s perspective, the future is bright for CLL treatment.

 

MK       You know, one of the things that I tell people is that I don’t plan to retire until CLL is cured, but I think that we already have sub-sets of patients that have been in continuous remission for ten-plus years, so that functionally or operationally, a number of these patients are already cured. And I think that when we explore some of these new drugs, either by themselves or in novel combinations, I think that we will continue to double the expectation of survival of patients that need treatment.

 

The other area that I think will come into play is because most of the things that we had available to us, either were damaging to the DNA, or damaging to the immune system, but early intervention was not a good option. I think that we now have models to predict the likelihood of patients needing treatment, and I think we’ll have early intervention with some of these oral medications, that don’t damage DNA, and don’t damage the immune system.

 

DS       Excellent, Dr Keating thank you very much, very interesting.

 

MK       Thank you very much Dr Smith.

 

DS       It was a pleasure.