MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas, M.D. 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. Today our subject is lymphoma: in particular mantle cell lymphoma. And I have 2 guests to talk about that today. They are both from M.D. Anderson's Department of Lymphoma and Myeloma. We have Dr. Jorge Romaguera who is a professor and Michael Wang who is an associate professor. First of all, let's start with the basics. Let's talk about there are 2 types of lymphoma. We have Hodgkin's lymphoma and then a whole group of lymphomas that are non-Hodgkin's lymphoma. So mantle cell Dr. Romaguera is a non-Hodgkin's lymphoma.
Dr. Jorge E. Romaguera: Yes, it is a non-Hodgkin's lymphoma. Lymphomas in general are about 40 subtypes and they are divided between Hodgkin's and non-Hodgkin's lymphoma. Most of them are in the non-Hodgkin's category and one of those is mantle cell lymphoma.
Lisa Garvin: Lymph glands are obviously -- there are lymph glands or nodes through your body and the lymph fluid travels through and the lymph carries like -- lymphocytes that help us fight disease and so forth. Doctor Romaguera, tell me exactly where the mantle cells are in a lymph node.
Dr. Jorge E. Romaguera: One of the main ways of differentiating the 40 or so subtypes of lymphoma is how they look under the microscope and the mantle cell is derived from a zone called the "mantle zone" which is located on the outer portion of the follicle. The follicle is the main ingredient of the lymph nodes. The lymph node is composed of many follicles. And that is where the mantle zone -- mantle cell lymphoma derives its name from.
Lisa Garvin: And it's pretty rare as non-Hodgkin's lymphomas go, it's fairly rare isn't it?
Dr. Jorge E. Romaguera: It's about 6 percent of the non-Hodgkin's lymphomas.
Lisa Garvin: Do you -- do we see a lot of mantle cell lymphoma here at M.D. Anderson because we're a big cancer center Dr. Wang?
Dr. Michael Wang: Yes, we -- mantle cell lymphoma as Lisa as you point out is a rare disease in the community. But it is very a common disease. It is the focus of our clinical and translational and basic research of our group especially with Dr. Romaguera and me. We are focusing on mantle cell lymphoma. Because we are very wide -- big referral center and although it is rare in the community but we see mantle cell lymphoma everyday in our daily practice. It is a very common tumor for us.
Lisa Garvin: And it's typical -- what is the typical population affected by mantle cell...
Dr. Michael Wang: The typical -- anywhere between -- the statistics vary. The 6 percent is an international population. Actually Dr. Romaguera and I did a 30 year incidence in the U.S. by the SEER - S.E.E.R. - data that try and summarize the 30 year experience in the U.S. population with mantle cell lymphoma affected. Our calculation was about 3 percent. So the data varies between 3 to 6 percent that people were diagnosed is a between -- anywhere between 4 thousand to 10 thousand people each year with this disease. It depends on the data.
Lisa Garvin: And the typical patient is...
Dr. Michael Wang: Typical patient is a person with around 65 years old in male who is Caucasian and of course you know there is ladies. There's African Americans and Asians and other populations. Typical is a 65 year old gentleman: Caucasian gentleman with lymph nodes.
Lisa Garvin: Now how do these patients generally present because a lymphoma is like leukemia. It's not really a solid tumor per se so how do your patients generally present? Do they come in complaining of flu like symptoms? Or how do they generally get diagnosed?
Dr. Jorge E. Romaguera: Actually only about 20 percent present with symptoms such as fever or sweats or weight loss. The sweats would have to be drenching to be called sweats due to lymphoma. Most of them all they feel a lump somewhere in the body: usually the neck or under the arms, maybe in the groin. Or what we're seeing more and more often is they go to the doctor's, they did a blood count and they saw that the lymphocytes were higher. And then they do a special test called the flow cytometry test to detect the population of lymphocytes. And they can tell that there is a clone of cells of those lymphocytes. They're all coming from the same mother cell if you want. And that's one of the criteria in lymphoma for calling something a lymphoma. They usually are all what they call monoclonal. They come from the same cell. And you can detect that in flow cytometry when you do the test in the blood.
Lisa Garvin: Now lymphomas are staged slightly differently from solid tumors. You have like an indolent group which is slow growing. And then you have an aggressive group but then you have other criteria as well. So explain how you stage it.
Dr. Michael Wang: Mantle cell lymphoma just as we described in the paper published in 2008 in Caser [phonetic] is actually publicly available. In that over 90 percent of the patients present at a stage 4. Therefore stage -- very few patients presented at early stages. So mantle cell lymphoma occurs. It's an [inaudible] disease it's usually discovered late in the phase.
Dr. Jorge E. Romaguera: Actually yeah. This staging system that we started to use in mantle cell for lack of a better staging system although now we are using other criteria was an old staging system devised in the 1980s for actually for Hodgkin's stage 1, 2, 3, 4. And 4 was anything outside the lymph nodes: extra nodal. And it just so happens that practically all mantle cell lymphomas have some involvement of the bone marrow which by definition is an extra nodal site. So even if they have nothing elsewhere, no lymph nodes, they're automatically a stage 4. Also about 90 percent of the mantle cell patients have the disease in their small -- in there large intestine although mostly without symptoms. But if we -- you look for it and do a colonoscopy and biopsy even if you don't see polyps, you will find microscopic disease. Why? We don't know.
Dr. Michael Wang: We would like to share with our audience that mantle cell lymphoma is although a deadly disease, if untreated it is rapidly fatal. But therapies has been changing the patients' life for many, many years. We started the top therapy -- our top therapy is old standard. Dr. Romaguera in 2005 pioneered the study further. [Inaudible] alternating with a [inaudible] therapy. That response rate is over 97 percent. The complete response is nearly 90 percent. Dr. Romaguera and I did a 10 year follow up with the data. Is after 10 years, many, many people survived. And it -- but mantle cell lymphoma is considered not curable but we have so many clinical agents. Mantle cell lymphoma is one of the most rapidly advancing fields in the field of lymphoma and the [inaudible] hematological diseases.
Lisa Garvin: So the goal in treating mantle cell lymphoma is not really a cure but managing the disease? Or I mean, what is the end goal here if it's not completely...
Dr. Michael Wang: Number 1, improve the patients' survival. Number 2, decrease their suffering and improve the quality of their life. Mantle cell lymphoma will be cured. It's a matter of time. And we are making so much progresses at this point that we do have so many good drugs, good agents that meeting survival is increasing every -- almost every few -- short time we'll have new survival data.
Lisa Garvin: And Dr. Romaguera, you were saying that actually the survival rate has jumped by about a year or 2 years just in a short time.
Dr. Jorge E. Romaguera: Right, the -- 2 or 3 years ago the [inaudible] published data showing that the more aggressive regiments improved survival by -- and in general the quoted survival is 5 to 6 years versus 3 to 4 which was 10 years ago. I believe that's in part due to the addition of antibodies like [inaudible] that's called now chemo immunotherapy. And I think we're also getting a better handle of it. Not all mantle cells are very aggressive. There is a system now. There is a staging -- not a staging necessarily but a risk model that determines in many situations and this has been confirmed you now, how aggressive the tumor will behave down the road. So we are able to diagnose patients earlier. And I think that in part explains that we can track them longer and our survival has improved.
Dr. Michael Wang: I'd like to share with the audience that there's a concentrated knowledge at M.D. Anderson that has been going on for -- been in the development for many years by many generations of clinical and the basic research. And we have -- our contribution from our group at M.D. Anderson -- all mantle cell lymphoma has been instrumental and critical in each step of the clinical and the basic research development. Dr. Romaguera and I are the main but we are not all. We have the mantle cell lymphoma program [inaudible] is actually comprised of many colleagues from stem cell transplant. Dr. Champlin are the Chairman of Stem Cell Transplantation because mantle cell lymphoma has to be treated with a chemotherapy and trans stem cell options. Dr. Larry Kwak - our Chairman of the Department of Lymphoma-Myeloma - is also part of this mantle cell lymphoma program. But we have also Dr. Fredrick Hagemeister: people who has been working on [inaudible] mantle cell lymphoma for many years. We have a big group. But this is not all. We have many colleagues in the laboratories research doing the [inaudible] work. They have been focusing on their careers. And our group have many, many people. Researchers, [inaudible] plus doctors, associate professors, full professors whose lives are -- whose main focus area is mantle cell lymphoma. But we wanted to translate this into clinical medicine and I would like to share you a brief moment later what is in the making.
Lisa Garvin: Well and this seems to be -- there's several -- there's like monoclonal antibodies. There's other targeted therapies. So the new more sophisticated or personalized chemotherapies seem to be a good fit for lymphoma treatment.
Dr. Michael Wang: That's exactly what's going on. For example, there's -- [inaudible] has already made a -- the monoclonal antibody and [inaudible] already made history. It's part of the standard therapy and mantle cell lymphoma is incorporated in the [inaudible] program. What's after that was called [inaudible]. [Inaudible] is also -- belongs to a class of [inaudible] inhibitors. It's FDA approved just for mantle cell lymphoma. That is relapsed after the [inaudible]. So this is the drug. This is not approved for other lymphomas but only approved for mantle cell lymphoma. This approval not only brought a new option to the patients, but also make -- together with other development made mantle cell lymphoma a [inaudible] target for new drug therapies to test. As a result, many other drugs are being tested. For example, the talk of the day is called the [inaudible] inhibitor. This is an oral pill that takes once a day. I prevented -- or M.D. Anderson is a leading institution for this international [inaudible] trial. Dr. Romaguera and I together with many other colleagues did this trial. I presented it at the American Society of Hematology in December in 2011. It was only in a single agent oral drug that has minimal side effect. The response rate is already 80 percent. Many of my patients are still on the trial after more than 1 year of therapy. And they have good quality of life and their blood counts are not terribly affected. As a result, our institution is again leading an international trial to try to get this drug to be FDA approved so that it will be available to the patients in the United States and also America and in the future to the world.
Lisa Garvin: And what is life like for a mantle cell lymphoma survivor? I mean it sounds like it's a life of constant surveillance. I mean it sounds like they would have to pretty much have a relationship with their oncologist the rest of their life.
Dr. Jorge E. Romaguera: Yes, they have to be -- we have to be monitoring them. If we achieve a complete response -- clinical complete response with the therapy that we give and we finish the treatment, we still have to do x-ray studies every 3 months for a year, every 4 for the next 2, every 6 for the next 2 because we know at some point it will show its face and hopefully by then we'll have another drug that is easier to take, that is less toxic and can control the lymphoma for as long as possible. So we go from drug to drug trying to keep them alive with good quality of life.
Lisa Garvin: And would you say similar to our leukemia patients here that probably about 85 percent of leukemia patients are on some sort of protocol. Is that also true with mantle cell lymphoma?
Dr. Jorge E. Romaguera: We strive to make the protocols that we have accessible to them sometimes because they live far, far away in another state and the protocol requires for them to be close to us. Unfortunately we can not offer that trial to them. Some of them actually make a huge commitment and stay in Houston for 6 months to get the drug. It depends. The [inaudible] kinase inhibitor for example which is a pill, it allows you to go back and forth but you still have to come to Houston every -- at least every month you know down -- after the first few weeks of the trial to be monitored and to get your next month's supply of the drug which you can only get here because of the pharmacy arrangements.
Dr. Michael Wang: So I think I could use an example to tell that the audience what the patient with mantle cell lymphoma life is. We have an elderly gentleman who was over 10 years ago was diagnosed with mantle cell lymphoma at the age of 75. He's from Boca Raton. I would be able to reveal his name. But at the time of diagnosis he was told, "Don't buy any green bananas."
Lisa Garvin: [laughter]
Dr. Michael Wang: It's not going to grow and survive very long. But he came to M.D. Anderson and got on Dr. Romaguera's protocol [inaudible] that. He stayed in the Anderson for more than 6 months in the Rotary House and he went into complete remission. Thereafter he followed with me once every 4 to 6 months and 3 very good years of quality of life. Then the disease came back. He was treated by an FDA approved the drug called [inaudible]. He went into again a complete remission 2 years. Every 4 to 6 months he comes back but he was -- then he relapsed again. We put him on the trial called the [inaudible]. It's a [inaudible] agent with the monoclonal antibody called [inaudible]. He went into another remission. And thereafter about a year later, he relapsed again and we give him more drugs and we put him on the [inaudible] kinase inhibitor. Two days ago he celebrated his 86th birthday. He has 6 grandchildren. After his therapy started 10 years ago. And he is in 15th month of [inaudible] kinase. Was only on it once a day. He is in complete remission. He is the eldest patient on this trial: 100 patients internationally. He is doing quite well.
Lisa Garvin: Wow. I mean for 86 a lot of people would say something else is going to kill me first before the lymphoma. How often do people need a stem cell transplant? Is it -- is that -- you know, half the time?
Dr. Jorge E. Romaguera: So the face of treatment for mantle cell lymphoma went from treating it as an indolent to being very aggressive including [inaudible] plus or minus transplant. And now they have this model where they try to predict who might be very slow growing and might not need immediately a very intense therapy. For those that we think need the intensive therapy, the option of transplant is one usually after treatment of several rounds of chemo therapy to shrink the disease. I personally like as a [inaudible] chemotherapy [inaudible]. There are others. Most places that do aggressive therapy [inaudible] initially, they consolidate with the stem cell transplant: usually the patient's own stem cells. However, we at Anderson have been doing since 1994 -- well actually the protocol started in 1998 without transplant. Only [inaudible] alternating with [inaudible] and we still don't do transplant consolidation in patients that achieve a complete remission to our front line or [inaudible]. And we have very good results: as good as any transplant. So some other institutions are following our lead but I would say many others consolidate with a stem cell transplant. So right now there's no clear winner between consolidation stem cell transplant or if [inaudible] completely responded to our [inaudible]. Just do 6 to 8 rounds of that which is aggressive enough. And don't do consolidation stem cell.
Lisa Garvin: Interesting. So is that one of your end goals maybe to nullify the need for a stem cell transplant which can be you know very invasive? They have to be in a protected environment and so on and so forth.
Dr. Jorge E. Romaguera: Actually that's what our current front line study is trying to achieve. As Dr. Wang stated, our complete remission rate in general is very high. Actually it's 87 percent overall even in patients over 65. They have like an 84 percent complete remission. So our goal by adding [inaudible] the [inaudible] inhibitor to the [inaudible] is to prevent those patients that are recurring down the road. So our goal in this new trial that we've started about 2 years ago is to prevent those recurrences. We're already having a very high complete remission rate but maybe we can prevent those -- that evidently were not in complete remission, they had some cells that we could not detect and that's why they went on to have recurrence years later.
Lisa Garvin: Well it sounds like in closing that there's a lot of hope on the horizon for -- oh 1 final word from you Dr. Wang.
Dr. Michael Wang: We would like to invite all the patients at any stage with mantle cell lymphoma to come to M.D. Anderson to see us. We have numerous continuing trials. We just named only a few of them. To name a few more for example: our new generation [inaudible] inhibitors. After [inaudible] there's [inaudible]. We have a clinical trial ongoing. We have the nuclear protein [inaudible]. That's about to open for mantle cell lymphoma. We have [inaudible]: our [inaudible] kinase inhibitor. We have MKT. We have numerous clinical trials. We welcome patients at any stage to come to see us. We are dedicated to provide and try to provide good results.
Lisa Garvin: I couldn't have said it better myself. Thank you both for being with me today. If you have questions about anything you've heard today on Cancer Newsline, contact Ask M.D. Anderson at 1-877-mda-6789 or online at www.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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