Kinase Inhibitors Offer New Hope for Mantle Cell Lymphoma

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Andrew Schorr:

Dr. Martin, where are we now in the treatment of mantle cell lymphoma? 

Dr. Martin:

Well, mantle cell lymphoma has notoriously been a pretty challenging lymphoma.  It’s pretty rare, so research has been slower maybe than other more common lymphomas like follicular lymphoma or large-cell lymphoma.  The other thing that’s challenging about it is that it shares some characteristics of aggressive lymphomas and that people acquire chemoresistance fairly quickly, and like indolent lymphomas it’s not curable.  So you combine those two things and you end up with a disease that makes it challenging for patients and physicians alike. 

Historically the standard of care for frontline people, treatment of patients with frontline mantle cell lymphoma has been R-CHOP, but I think everyone has agreed that that’s maybe not a satisfactory treatment with an average progression-free survival of only about 18 months, so there’s a lot of room for improvement.  And that improvement I think has taken a long time for now partly because our understanding of the disease has been limited, so we’ve sort of fallen into that standard oncology trap, you know, where drugs that we have don’t work really well so let’s just give more of them, right? 

So regimens like hyper-CVAD or autologous stem cell transplantation have really become standards in younger patients that can tolerate those therapies, and they clearly have activity and can prolong significantly response durations.  But they come at an expense, and that expense is significant toxicity.  And it’s only more recently that as our understanding of the disease biology has been improving that I think newer and more exciting treatments have become possible. 

And I think one of those treatments that’s going to be the most exciting over the next few years is a drug from a company called Pharmacyclics.  The drug is PCI-32765.  It’s an inhibitor of an enzyme called BTK or Bruten’s tyrosine kinase, and basically what BTK does is it’s an enzyme that transmits a signal from the surface of the cell to the cell nucleus and that signal tells the cell to continue to divide.  And so this drug, PCI-32765 is an oral drug administered once a day.  And in a phase 1 study that was presented here last year there were seven patients with mantle cell lymphoma and--I believe it was seven, and five of seven responded, which was of course very encouraging, you know. 

So this is compared to bortezomib which is the only approved drug and has about a 30 percent response rate in mantle cell lymphoma. 

So granted this was a small number of patients but very encouraging, right?  Particularly given the fact that the drug was so well tolerated.  It has minimal GI toxicity, very limited lowering of blood counts, almost nothing.  So it’s almost as if people are taking a blood pressure pill, right?  And the company has moved forward with a phase 2 study, and preliminary results of that study will be presented here on Monday.  And with 48 patients enrolled, I think about half of them evaluable, many of them having received prior aggressive therapy, their response rate is in the 60 to 70 percent range.  It’s too early to say how long those remissions are going to last, but certainly very encouraging, and I think that that approach will be the future of mantle cell lymphoma.  As we improve our understanding of the biology of the disease we will be able to come up with better treatments, and this is just the tip of the iceberg, I hope. 

Andrew Schorr:

How can patients gain access to this investigational therapy? 

Dr. Martin:

So this is right now an ongoing phase 2 study.  It’s an international study in North America and Europe, so it will be moving very quickly, which I think is a testament to the fact that people are excited about the drug.  I believe that the company is considering a phase 3 study, which will hopefully be available very broadly.  In the interim there may or may not be some investigator-initiated trials available. 

Andrew Schorr:

So it would seem it’s important for patients to ask about it. 

Dr. Martin:

Absolutely.  Clinicaltrials.gov is a challenging website to use.  Patient organizations such as yours, Leukemia Lymphoma Society, Lymphoma Research Foundation can often help steer patients to these trials. 

Andrew Schorr:

So you say this is just the tip of the iceberg and there are other potentially promising therapies to come? 

Dr. Martin:

Absolutely.  I think we’re looking more for now some rational combinations.  So BTK inhibitor works in 60 to 70 percent of people.  Why doesn’t it work in everybody?  When it doesn’t work or when it works and patients relapse, what are those changes?  And as we start to understand those things we may be able to make them work even better. 

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