MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancer Newsline. A podcast series from The University of Texas: MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin, and today our guest is Dr. Jason Westin. He's an assistant professor in our Lymphoma and Myeloma Department and we are going to be talking about non-Hodgkin's lymphoma. Welcome Dr. Westin.
Dr. Jason Westin: Thank you Lisa.
Lisa Garvin: And lymphoma, I always like to call it one of the microscope diseases because, you know, you really only diagnosis these under a microscope and it all has to do with what the cells look like. So what is lymphoma?
Dr. Jason Westin: That's exactly right. This is a microscope diagnosis, I agree with that term. Lymphoma is a genetic aberration of normal immune cells. So these cells live in the lymph nodes generally, hence the term lymphoma. These are lymphocytes that have gone wrong. And so lymphoma is a catch-all term that includes something about 40 diagnoses subtypes. There's non-Hodgkin's, which is what I think we're talking about today, and Hodgkin's. And non-Hodgkin's is about eight times more common than Hodgkin's lymphoma. In 2012, there was an estimated 70,000 new diagnoses of non-Hodgkin lymphoma. It's the seventh most common type of cancer both in men and women. And in 2012, unfortunately, there were about 19,000 estimated deaths to occur from non-Hodgkin lymphoma.
Lisa Garvin: It's typically a disease of middle age, is it not?
Dr. Jason Westin: Middle age and into the 50's and 60's it's, Hodgkin's lymphoma often is younger patients, non-Hodgkin's is often older patients.
Lisa Garvin: And that's what the differentiation was, why we have Hodgkin's here and then all of them lumped into the other category?
Dr. Jason Westin: That's right. And Hodgkin's was initially diagnosed after a physician, named Dr. Hodgkin who had a number of young patients that had a particular type of disease named after him; it was one of the first diagnoses that we made with a microscope. Non-Hodgkin's often was confused for that, but as we've gotten more sophisticated we've been able to tease out the name, so that's why it's called non-Hodgkin's, it was the other disease when we already knew how to diagnosis Hodgkin's.
Lisa Garvin: Now symptoms for lymphoma are kind of subtle aren't they?
Dr. Jason Westin: They can be. For some patients they are not. You often talk about people having drenching night sweats or fevers or weight loss, but that's really uncommon. Usually patients who have non-Hodgkin lymphoma have a fairly subtle presentation and they'll find a lump either in their neck or under their arm or in their groin. They'll have an insurance physical and their doctor will say, "What is this?" They'll have an x-ray for some other purpose and they'll show an abnormality, so often times it's found not necessarily because of some dramatic presentation, but from a relatively subtle finding.
Lisa Garvin: How often do you catch or what stage do you typically catch lymphomas in a diagnosis?
Dr. Jason Westin: That's a good question and it depends on the type of lymphoma. The very slow-growing lymphomas, we often refer to them as indolent lymphomas, often show up at an advanced stage and that's because they've been growing sometimes for months or even years before we know that they exist. Not having a significant symptom burden, the disease could have been there for quite a long time and can be multiple locations. The more aggressive lymphomas, the ones that grow more rapidly, generally could be found at an earlier stage because they cause more symptoms early on.
Lisa Garvin: Now, and of course as we've said, you know, diagnosis is really key here because you have to get a handle on exactly which type you have.
Dr. Jason Westin: That's right, that's right.
Lisa Garvin: Okay.
Dr. Jason Westin: So that's it. That's a critical factor and having an expert hematopathologist look at a biopsy specimen is essential for non-Hodgkin lymphoma. As we mentioned earlier, there are a lot of different subtypes and the treatments ranged fairly dramatically from subtype to subtype. So having a confident diagnosis, being assured of the correct subtype diagnosis is essential for this disease. Lymphoma was one of the first diseases where we really began to subtype cancers, and we're seeing this now more and more as we get more sophisticated with our ability to diagnosis cancers. In the solid tumor world, we're beginning to notice that some cancers have a particular mutation or a particular aberration that we can target with a new drug. In the lymphoma world, we found this quite early on that we can subtype these diseases based on protein expression on the surface or in other things that pathologists can subtype based upon what they saw under the microscope. So, lymphomas were some of the pioneers along with leukemia in terms of subtyping these into relative therapeutic categories.
Lisa Garvin: So typically lymphoma is a disease that's treated with chemotherapy, it's not really a tumor mass that you're removing, but is stem cell transplantation also used as a treatment option?
Dr. Jason Westin: Stem cell transplantation can be used as an option, but generally it's reserved for patients that have had not an acceptable response to initial treatments. So the disease basically has come back and we think that it's likely to come back again and again. So stem cell transplant is a fairly aggressive treatment that does play a role for lymphomas, but generally it's not in a frontline setting and reserved for select cases.
Lisa Garvin: So as a systemic disease, typically they're on regimens of chemotherapy, but does surgery or radiotherapy play a role?
Dr. Jason Westin: That's a good question. I often get asked that. Generally the answer is no as a sole mechanism of treatment. Back when we knew how to diagnosis Hodgkin's and not much else, before we had adequate chemotherapies, surgery and radiation were the primary mechanisms of treatment for lymphomas. And what we would find is that we would do a surgery to remove an enlarged lymph node and think that we had, "got it all," and then not very long afterwards, a lymph node next door would pop up. Same for radiotherapy. We'd radiate an enlarged lymph node and very shortly thereafter we'd see another one pop up so we think that in the majority of cases, radiation or surgery alone generally just delays effective systemic treatment. They can play a role, generally more radiation than surgery can play a role to target a very large tumor after chemotherapy to try and consolidate or improve the benefit from initial therapies, but by themselves localized therapies like radiation and surgery are not generally effective.
Lisa Garvin: And recurrence is a big issue with lymphomas or certain types, isn't it?
Dr. Jason Westin: That's true. The indolent lymphomas, the slow-growing lymphomas, have a relapsing pattern where they often respond to our treatments, they're very sensitive to our treatments, but they majority of patients have a relapse of their disease at some point in the future. That relapse, is again, sensitive to treatment for the majority of patients so it's a disease that's treatable, but not generally thought to be curable with our current technologies. The more aggressive lymphomas hopefully will not come back, because if they come back they're often not as treatable the second time around. And that's a situation where we could consider using a stem cell transplant to try and consolidate benefit.
Lisa Garvin: So lymphoma, much like leukemia, would be a perfect target for molecular therapies and I know you've got a lot of exciting things going on in that arena. Talk about some of the new receptors or targets of these drugs.
Dr. Jason Westin: Yes. There's a lot of excitement in the clinical trial world for lymphomas. One of the most promising recent targets that we've gone after in B-cell lymphomas is the B-cell receptors signaling pathway. And this is something that all B-cells have and are basically required to have for survival as an active B-cell receptor. And the wiring from the B-cell receptor downstream has a number of potential targets that [inaudible] drugs they can hit. One of the most promising ones that's been featured recently at a lot of important meetings, such as the recent ASCO 2013 meeting, is a drug called ibrutinib. And what this drug does is targets a protein called Bruton's tyrosine kinase. And Bruton's tyrosine kinase was initially identified in a number of rare disease types of a number of families that basically lacked B-cells. These young children had very frequent infections and a doctor named Bruton found these patients and identified the aberration they had and it was named after him. So Bruton's tyrosine kinase is a critical protein for B-cells to have. And if that lack it, the B-cells are not able to function. So this drug is an oral medication that targets the wiring of the B-cells and has shown very significant activity in a number of lymphoma types, including the ABC subtype of large-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. And it's actually recently received the FDA breakthrough designation.
Lisa Garvin: And lymphoma, the lymphoma patient population is particularly poised to benefit from clinical trials of these diseases because it seems like a lot of drugs are often fast-tracked because the preliminary results are so good.
Dr. Jason Westin: That's very true. So lymphomas and generally are fairly sensitive to treatments. It's a difference from solid tumors where response rates are quite low from targeted therapies and we have to tease out the exact relevant subtype. In lymphomas, most patients respond to treatment. The disease may come back, but they're initially sensitive. So having a targeted therapy in a disease where we have sensitive population, the effect size can be quite large, so you're right. We are, not only do we have the ability to find these targets, but when we find them, they're actually effective.
Lisa Garvin: Would that be your suggestion though that people with a lymphoma diagnosis seek out clinical trials?
Dr. Jason Westin: I think so. I think the, there was a discussion at the recent ASCO meeting that only approximately 3 percent of cancer patients, go on to clinical trials, which I think is a tragedy because those patients are the only ones that contribute to our knowledge about tomorrow's treatments. The patients who go on to standard treatments may get benefit, but we don't learn anything from that in the sense of how to improve upon our current therapies. So, for example, the most common subtype of non-Hodgkin lymphoma, the most common type of lymphomas in general, is called diffuse large B-cell lymphoma and the standard treatment that patients who are not on clinical trials receive for diffuse large B-cell lymphoma is something called, Art Chop. C, h, o, p. And this combination of chemotherapy drugs was initially developed in part here at MD Anderson in themed 1970's, and if you go back and look at the initial paper that describe this chemotherapy regimen, there is literally no change in any of the chemotherapy drugs since 1976. The only change has been the addition of rituximab, an antibody that targets B-cells. So people who are not going on clinical trials are, in a sense, getting a treatment that's 35-years-old, that's not acceptable when we have targeted therapies. So I think accrual to clinic trials is essential for us to improve upon our current therapies.
Lisa Garvin: I think that's a perfect note to end on. Thank you Dr. Westin.
Dr. Jason Westin: Thanks Lisa.
Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact Ask MD Anderson at 1-877-MDA-6789 [music] or online at mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.
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