An Evolving Treatment Landscape: Mantle Cell Lymphoma Treatment and Research News From an Expert

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Topics include: Treatment

Noted expert Dr. Stephen Douglas Smith, from the Seattle Cancer Care Alliance, joined Patient Power to share promising advances being made in therapies for mantle cell lymphoma. Dr. Smith discusses the evolution of the treatment landscape and exciting drug approvals to be announced the 2018 American Society of Hematology (ASH) annual meeting. Dr. Smith goes on to share clinical trial research on targeted therapies addressing specific biology of mantle cell lymphoma, toxicities and long-term effects of medicines, and patient response rates. Dr. Smith also explains distinct features of mantle cell lymphoma to ensure patients get an accurate diagnosis and the value of seeking a second opinion. Watch now to stay up-to-date with the latest treatment and research news.

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Transcript

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:

Hello and welcome to Patient Power.  I'm Andrew Schorr.  We're talking about mantle cell lymphoma, which is a B?cell lymphoma, one of the non?Hodgkin lymphomas.  And with us is an expert from the Seattle Cancer Care Alliance, hematologist/oncologist Dr. Stephen Smith.  Dr. Smith, thank you for being with us.  

Dr. Smith:

Thank you for having me.  And, as Andrew said, I'm here at Seattle Cancer Care Alliance and focus on mantle cell and other B?cell non?Hodgkin lymphomas as an associate professor at the University of Washington department of internal medicine, medical oncology division.  So that's the formal title.  

Andrew Schorr:

Right. Now, of course your center sees a lot of patients.  You're also a research center, so what we wanted to get at, Dr. Smith, is maybe what's changing and to give maybe new hope to people affected by mantle cell lymphoma.  

Dr. Smith:

Sure.  I think the change I would with categorize in three main ways.  First, we're seeing forward evolution of the drugs known at BTK inhibitors.  Those are so?called small molecules which bind an enzyme and turn that enzyme off that is overactive in mantle cell lymphoma cells. The first of those drugs we all know came about five years ago, but there's been a second drug approval last year in acalabrutinib, and this year at the American Society of Hematology meeting we'll have a lot more detail on a third BTK inhibitor called zanubrutinib, and so some initial data with follow?up on that newer drug.  And all of these drugs are having response rates that are high and have shown complete responses, which for a single pill in mantle cell lymphoma is new and an important advance.  

Andrew Schorr:

Okay.  So ibrutinib (Imbruvica), acalabrutinib (Calquence), maybe zanubrutinib.  So you've had a chemo approach that you've been using for years.  Would these drugs replace that?  

Dr. Smith:

Well, our main idea in mantle cell lymphoma is that chemotherapy has provided a typical set of what we would consider diminishing returns in mantle cell lymphoma. That is, with each chemotherapy treatment we may expect a shorter remission or less probability of getting a remission.  So in combination with that we know that mantle cell drop lymphoma affects older adults frequently in whom intensive therapies are riskier.  So due to those facts we have to come up with better therapies that can sort of bypass chemotherapy toxicities and address the specific biology of mantle cell.  Those are generally tested in the second? or third?line or later setting, and then moved forward towards first?line treatment.  

 

So we're working on moving these BTK inhibitors and other treatments earlier in the course of the disease when they may have even higher efficacy and greater promise. 

Andrew Schorr:

You use this phrase, "other treatments."  Patients have been following treatment in blood cancers have been hearing about CAR?T cell therapy, chimeric antigen receptor T?cell therapy, where I believe you can engineer a patient's own T cells to try to fight the cancer.  Will this have a place in mantle cell?  

Dr. Smith:

It's very likely. There are now specific trials geared towards CAR?T therapy in mentality cell lymphoma, and in the existing data sets of what we would consider all comers, B?cell non?Hodgkin lymphoma trials of CAR?T therapies, we have seen promising results in mantle cell lymphoma. So we have early signals that mantle cell lymphoma may respond effectively and in a prolonged fashion in CAR?T cell therapies, but we need the dedicated trials to mantle cell lymphoma, which, as you know, can take some time to accrue given the uncommon incidence of the condition.  But that is our next main step, and there is good reason for optimism with CAR?T cell therapy.  

 

And, as you said, there are multiple different targets that can be addressed too on the surface of the mantle cell.  So mantle cell has a unique phenotype.  It has B?cell markers, but it also has other markers which can be addressed effectively by CAR?T cells, and so those are all being addressed with the current trials. 

Andrew Schorr:

Now, of course, you mentioned about the BTK inhibitors.  So explain a little bit about how they work.  What are they targeting?  And also you talked about some advantage that may appear with them, but what about side effects as well?  

Dr. Smith:

Sure.  The BTK again refers to an enzyme that is I would just simplify by saying it's overactive in mantle cell lymphoma.  It is what we would say constituently active, telling the cell to continue its pro?survival and growth activities regardless of any external signal, and that's a sign that it is a driver of the mantle cell lymphoma biology that needs to be stopped.   

The BTK drugs are an interesting group.  They have different levels of what we call specificity.  So some bind mostly to BTK and less so to other kinases in the cell, and others are what we would consider more promiscuous drugs in that they can had hit multiple different kinases inside the cells and in other cells.  So the main issue with BTK inhibitors is that they appear to be similarly effective, each of the three versions we see but with slightly unique side effect profiles.  And by hitting other kinases they can trigger things like platelet dysfunction, bleeding, low blood counts and possibly even risks such as atrial fibrillation which has been well described with ibrutinib.  

Andrew Schorr:

I know some people with ibrutinib have had some kind of muscle pain and also even stomach issues.  Many people are doing well, but it would seem like if this more targeted therapy can work it could be preferable to the, as you said, the diminishing returns of chemotherapy.  

Dr. Smith:

Absolutely. And I think we're seeing again refinements in these medications, longer follow?up that gives us a good idea of safety data.  We're seeing real?world use of these drugs so that you have one answer that is available from the clinical trial but when you use the drug in reality what do you see? How many patients can tolerate the drug for two years?  And we're seeing really critical data now that is more mature about long?term tolerability of these drugs.  

Andrew Schorr:

Okay.  So all of this, the approved drugs obviously have completed clinical trials, but I'm sure research goes on.  You mention one that is still in research, and you alluded to other research going on.  So should people with mantle cell inquire about clinical trials for their condition? 

Dr. Smith:

Yeah, I think, you know, there's huge debate as to even how to treat mantle cell the first time around.  We'll see at ASH this year, at the American Society of Hematology meeting, we'll see some more data on new promising first?line combination treatments for younger patients headed toward an autologous stem cell transplant, but even that topic is very debatable.  And so first?line trials are very appropriate for mantle cell lymphoma, even though we think of sort of the first treatment as one we'd like to be tried and true and well defined, in mantle cell lymphoma there's a long history of extrapolation from other lymphomas. And so it's very appropriate to focus on a disease?specific opportunity to participate in a trial, both in frontline and later treatments. 

Andrew Schorr:

So, Dr. Smith, many people are not treated at the Seattle Cancer Care Alliance or other big university centers but may go to at least first a community center. What testing is important so that someone gets an accurate diagnosis?  

Dr. Smith:

Well, there is a somewhat of a complicated differential diagnosis for mantle cell lymphoma.  It has to be distinguished from other variance of B?cell non?Hodgkin lymphoma, and if there's a question referral for at least a review of the pathology slides at an academic institution is probably wise. 

 

Now, that being said, there are certainly features of mantle cell which can let you nail that down, and those are just established with a staining for a protein called cyclin or the genetic test that looks for a certain chromosome swap called a translocation (11;14), and if those are found the diagnosis is fairly secure, but there can be variance, and there can be a need for a second set of eyes so to speak on the actual biopsy tissue.  

Andrew Schorr:

So if mantle cell is suspected is this one of these more rare conditions where it would be a good idea to seek a second opinion?  

Dr. Smith:

Yeah, I think so. As I alluded to earlier, even the first set of treatments for mantle cell is sort of up for debate, the role and appropriateness of stem cell transplant and whether there are any trials that make transplant or first?line treatment even safer and better.  So I think because it's an uncommon condition with a variation—a set of options for first?line treatment, in this situation I am fairly positive and encouraging second opinions for the clinical or treatment side as well.  

Andrew Schorr:

Okay.  So with this research—and you're sort of at ground zero for it, and you mentioned this major meeting we have every year, the American Society of Hematology and papers being presented about it—for people who are watching and who are living with this are you hopeful that we are doing better and can do even better than that?  

Dr. Smith:

Yeah.  I always just think about the patients including the ones I talked to today and yesterday, I think it's very obvious that we're doing a lot better in mantle cell lymphomas.  We're getting a lot better at sequencing therapies, at making combinations which spare side effects that used to be routine and unfortunate, especially with repeated chemotherapies.  We are finding the right time to inject our cellulars, CAR?T cell therapies on trial basis.  And I think there is just a sort of transformation that's happening in mantle cell lymphoma where, you know, it may take us a few years to realize how far we've come just for data collection purposes, but it's very obvious in my day?to?day that we've come quite a long way even over the last three to five years. 

Andrew Schorr:

Oh, that's great news, very hopeful.  Well, of course, we'll keep in touch with you and you're peers who treat mantle cell to continue to inform the patients and their family members who are so concerned about this.  But the good news things are changing.  The oral therapies you mentioned that come into play, learn better how to use them, having more of them so that each patient can get what's right for them.  

And also, myself having been in two clinical trials, I'd urge people to consider that so you can partner with people like Dr. Smith and move things ahead perhaps for you and for the community at large.  Dr. Stephen Smith from the Seattle Cancer Care Alliance, thanks for all you do for people with mantle cell, and we'll look forward to you keeping us updated.  

Dr. Smith:

Okay. Thank you, Andrew.  

Andrew Schorr:

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 7, 2018