Friday, July 6, 2012

Chronic Lymphocytic Leukemia – not much going on.

The other day I came across a little review of the treatment of chronic lymphocytic leukemia. This is not a terribly common disease. Only about 16,000 people are diagnosed in the U.S. each year. But, I saw a large number of people with this disease in my practice. The reason for this is that this is not a very deadly disease; patients tended to linger in my practice for a long time. In fact, since this is generally a disease of older people, with 70 percent being over 65, other diseases would often take them away before the leukemia could. Although for the most part it is incurable, many people with CLL live 20 or more years without needing therapy. But there is another group that has a more aggressive disease and should get treatment soon after they are diagnosed. When I was in practice we didn’t have any very effective drugs. We had drugs that could eliminate most of the leukemia cells, but never cure the disease. Eventually, the leukemia would come back in spite of continuing treatment. So when I saw this article, I assumed that there were new treatments and drugs to offer these patients, because I had seen preliminary reports suggesting breakthroughs. Wrong! Yes many new drugs have been developed, but none are particularly effective. The only one that seems to be useful is a drug called Rituximab, which is an antibody directed against a molecule on the CLL surface. But even this drug saved only a few more people when it was added to standard treatment, treatment that is not much different than what I used. And in the key study where this was discovered, most of the patients were much younger than average. The only breakthrough that has occurred in the last few years, is that we have new molecular techniques that are able to identify those patients whose disease would rapidly progress. And this is important, especially for younger patients since the newer treatment does help a few of them. And if they are really young, they might even be helped by very aggressive chemotherapy and a bone marrow transplant. But for most patients, who are older and have active disease, a disappointment! No breakthroughs like the one for people with chronic myelocytic leukemia (see my article on Kareem and CML) where we have found drugs that are life-saving. Sorry.

10 comments:

Edward Auxer said...

Dr. Kattlove, I suggest you google PCI 32765 or ibrutinib. This agent has shown itself very effective against CLL while having an exceptionally low toxic profile. It's far superior to rituximab.

Edward Auxer

Herman Kattlove said...

My philosophy of cancer treatment is that the drug needs to extend life. That means that it needs to be tested in a randomized controlled trial against the standard treatment to see if it extends life. Patients taking the new drug have to live longer than those taking the standard treatment.

Herman Kattlove said...

I need to add that I haven't seen and randomized clinical trials with ibrutinib but would be glad to review such information and comment on it in this blog if it is available..

Brian Koffman said...

Contrary to your take, there has never been a more promising time for patients with CLL, Low toxicity sea change therapies such as Ibrutinib, GS-1101 and other kinase inhibitors are entering phase III trials after extraordinary results in phase I and II trials. Lenilimamide, HDMP, ofatumumab, alemtuzumab, and bendamustine are already ofter patients new alternatives for disease control and long symptom free remissions. While I agree a trial that shows an advantage over the "gold standard" of FCR in survival is what we all want, it is unrealistic and unfair to ask patients to assume that all these game changing therapies will all ultimately fail. I for one, like you am waiting for the proof, but am very encouraged by the early data and like many patients with cancer, must make decisions with imperfect knowledge.
For a nice overview of the research on the new small molecules, please take a look at Blood June 19:
The B-cell receptor signaling pathway as a therapeutic target in CLL
Jennifer A. Woyach, Amy J. Johnson and John C. Byrd
Thanks
Brian Koffman MD -http://bkoffman.blogspot.com/

Herman Kattlove said...

Certainly trying newer treatments in patients who failed standard therapy is important and worth doing. But, the question that must be answered is whether patients are living longer. And also, what is the cost/benefit ratio, mainly side effects, but also dollars? By the way, there is no June 19 issue of Blood.

Brian Koffman said...

Here's the link to the June 19 online abstract:
http://bloodjournal.hematologylibrary.org/content/early/2012/06/19/blood-2012-02-362624.abstract

It is the combination of excellent outcomes and minimal adverse events that make these new drugs so appealing, especially in the elderly and in refractory disease, the exact groups the NIH trial is targeting.

I suspect these drugs will be very very expensive, but so is all non-generic cancer therapy.

Herman Kattlove said...

Thanks for the link. Fascinating work with many new agents that I hope will pan out. But, we still need trials to prove the value of these drugs, particularly in older patients, which was the focus of my blog. Another issue is that CLL is not just a disease of too many lymphocytes, but also one of abnormal immunity Many patients die of infection (certainly that was my experience) so a clinical response with a drop in white count may not mean that the patient will live any longer if their immune system hasn't recovered.

Brian Koffman said...

Herman,

Last comments.

The new agents are being studied in older populations due to their need for less toxic therapies. Data is immature, but promising. Only time will tell.

You are so right about the immune dysfunction in CLL being a big killer. That and auto-immune issues and cytopenias. All of these are made worse by most
present therapies, even if lab and scans look great. Revlimid may boost IGG levels but that has yet to translate into fewer infections. The new therapies are unproven but it hard to imagine that drugs that block B cell communication will improve immunity. Prophylactic antimicrobials help somewhat and IVIg is an expensive and impractical option of those in dire straits.

Thanks again for raising awareness of this disease and the great gaps in present treatment options.

Brian

bkoffman.blogspot.com

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dodo@lip cancer said...

how about Flavopiridol and
lenalidomide? people said that those have shown some good result for treat CLL. but I think, it need some time if we want drugs that really effective to eliminate them...