B-Cell Receptor Agents: Is This the Road to a Cure for CLL?

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Topics include: Treatment

What are B-cell receptor agents? How can they help in chronic lymphocytic leukemia (CLL) treatment? There are several new drugs, B-cell receptor agents, now in clinical trials. Could they be the start of a new age in the treatment of CLL? Dr. Susan O'Brien from the MD Anderson Cancer Center in Houston shared her thoughts from the 9th European Congress on Hematologic Malignancies in Lyon, France.

Watch now as Dr. O'Brien explains how the science behind these new drugs is promising for CLL patients.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Welcome to Patient Power.  I’m Andrew Schorr.

There’s a whole new category of promising drugs that are being studied.  They’re called B-cell receptors.  Well, what does that mean?  What’s the science behind it?  We wanted an explanation, so we took advantage of Dr. Susan O’Brien attending the 9th European Congress on Hematologic Malignancies and asked her if she would explain B-cell receptors. 

Dr. O’Brien:

BCR means a very different thing in CLL than it means in CML, we have to be careful about that.  In CLL, BCR is the B-cell receptor, so remember that CLL cells are B-lymphocytes.  And, the relevance of that is that when you stimulate the B-cell receptor, whether on a normal B-cell or a malignant B-cell, that provides a very strong survival and proliferative signal to the cell, encourages it, in other words.  So, in a B-cell malignancy it would be nice, potentially, to be able to interrupt that signaling and hope that that would have a good effect on the disease. 

However, once that B-cell receptor is stimulated, there are a number of enzymes, or kinases, that can then be stimulated, in kind of a snowball fashion, one to the other to the other.  So, in fact, there are a number of different enzymes or kinases that could be targeted within that BCR pathway. 

So far there have actually been three different kinases that have been targeted, where the drugs have been in clinical trials.  The first one was fostamatinib, which was targeting Syk, S-Y-K, and that’s the only one that’s actually published, but the reason you haven’t really heard anything about it lately is that the development of that drug was then moved to rheumatoid arthritis.  So, you haven’t really seen much else in the hematologic malignancies area. 

The ones that are being actively investigated, right now, in CLL are BTK inhibitors, and BTK are Bruton’s tyrosine kinase, which is again another kinase in that pathway.  And the second one where there’s a drug that’s in active clinical trials is the PI3K kinase.  And there is PI3 kinase, both targeting the delta isoform, which is being used in CLL.  There is a new one targeting the delta and the gamma isoforms, which is being developed in lymphoid malignancies, and there’s other PI3 kinase that are being developed in solid tumors because some of these kinases actually can be in other relevant pathways, too. 

So, there are quite a number of the kinases.  You can target them, and you could, potentially in the long run, if you have two successful drugs, think about even combining them and getting maybe more bang for your buck than just using one of them, but those trials have not yet been done because all of these drugs are fairly early in development. 

Andrew Schorr:

Dr. O’Brien could a single one of these promising drugs be a breakthrough, just like Gleevec was for CML? 

Dr. O’Brien:

It’s not like Gleevec for CML, because, in fact, if you look at the data that has been presented so far, in the relapse setting, most of those remissions are partial remissions.  In other words, we’re not getting people into complete remission.  Now, the caveat to that is, here you’re actually affecting the cell, but you’re interfering with one enzyme.  It’s not like, again, chemotherapy that comes in and kind of slams the cell.  What we’re seeing is, that the responses evolve slowly over time. 

Although I’m making the statement that there’s very few complete remissions, we are beginning to see complete remissions with longer follow-up, and so, I think, the jury is out on exactly what percentage of patients will be able to achieve a complete remission with just the single agent.  But it will take time.  That part is very clear. 

I think in the long run, what we want are complete remissions, because, if we’re going to try and cure people, we’ve got to get rid of the disease.  Partial remission is not getting rid of the disease.  So, my guess is that, yes, even if we can see complete remissions in a subset of patients with the single agents, I would hope, that by using combination regimens, the incidence would be higher, and we would see it much more quickly. 

Andrew Schorr:

So, is that the road to a cure? 

Dr. O’Brien:

Hopefully so.

Andrew Schorr:

As you heard, these B-cell receptors used alone or in combination, and they’re all part of the new age of CLL. 

Thank you for joining us.  I’m Andrew Schorr.  Remember, knowledge can be the best medicine of all. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on December 13, 2013