Diffuse large b-cell lymphoma

MD Anderson Cancer Center
Date: 09/23/2013


Lisa Garvin: Welcome to cancer news line a podcast series from the University of Texas MD Anderson Cancer Center. Cancer News Line 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 is an assistant professor in the MD Anderson lymphoma and myeloma department and our subject today is a particular type of lymphoma called diffuse, large B cell lymphoma and you said Dr. Westin that this is the most common type of lymphoma?

Dr. Jason Westin: That's exactly right this is the most common type of all lymphomas, it is the most common lymphoid malignancy in adults.

Lisa Garvin: And how many people get diagnosed a year?

Dr. Jason Westin:  It's somewhere in the neighborhood of 25 thousand to 30 thousand people each year diagnosed with diffuse large B cell lymphoma.

Lisa Garvin: Of those that are diagnosed every year with this lymphoma, how many people do not survive?

Dr. Jason Westin:  It's a good question; this is an aggressive type of lymphoma that requires therapy. There are some types of non-Hodgkin lymphoma that can be observed and do not need urgent therapy but large cell lymphoma needs therapy pretty soon after diagnosis. It's a disease where we have a pretty decent track record of treating people and somewhere in the neighborhood of 50 to 75 percent of people are long term survivors when they receive this diagnosis.

Lisa Garvin:  And so I know that lymphomas are classified as indolent or aggressive, so this doesn't have like an indolent phase?

Dr. Jason Westin:  No this does not, there are occasions where people have and indolent lymphoma it then transforms into a more aggressive but that's generally considered transform large cell lymphoma, we're talking mainly about a brand new diagnosis, de novo large cell lymphoma. That's the most common type of large cell lymphoma.

Lisa Garvin:  But are you catching these at an early stage?

Dr. Jason Westin: They are often found at an earlier stage than indolent lymphomas, indolent lymphomas generally are there for quite some time before symptoms develop and usually are found in the advanced stage. Large cell lymphoma can be found at an earlier stage. But stage is not that critical for this disease, therapy for the majority of people is the same whether they're stage 2 or stage 3 or stage 4 so finding it early is not something that's a critical factor for the treatment of this disease.

Lisa Garvin: And what are the typical chemotherapy drugs for standard treatment?

Dr. Jason Westin:  It's a great question; the standard treatment for large cell lymphomas is pretty uniform for all stages and all different patients. It's unfortunate but the standard therapy for this disease was developed basically in the mid 1970's has remained essentially the same since that time and it's a combination called CHOP. The letters...each letter represents a different drug C stands for cyclophosphamide, H stands for doxorubicin, it used to be hydroxydaunorubicin, O stand for Vincristine it used to be called Oncovin and P stands for Prednisone. This is a uniform therapy that's given to basically every patient with large cell lymphoma which is unfortunate because we've learned over the past decade or so that there are actually multiple different types of large cell lymphoma that have different responses to this therapy.

Lisa Garvin:  And CHOP from what I understand is one of the more aggressive chemotherapies with higher toxicity is that correct?

Dr. Jason Westin:  For many people it's a toxic regime, it's one that we've used a lot and we have certainly more toxic regimes, hyper-CVAD or EPOC these are different variations on CHOP that could be more toxic. CHOP is not a gentle regime but the majority of patients can tolerate it pretty well.

Lisa Garvin:  So I know that we talked before in other podcasts about molecular therapies and targeted therapies for lymphoma so what sorts of drugs are we either in clinical trials or actually using in the clinic for diffuse large B cell?

Dr. Jason Westin:  It's a good question we really aren't doing as well as I think we need to in terms of incorporating new drugs in the front line setting. Right now CHOP is the standard and it's the really uniform therapy for everyone and what we're doing now is adding drugs to CHOP here and there but not looking at moving beyond CHOP or treating these subtypes of the disease as separate diseases. At the American Society for Hematology meeting in 2011, Dr. Lou Stout who is a pioneer in the field of large B cell research described these two subtypes of large B cell lymphoma, the ABC subtype and the GCB subtype to be as similar to each other as AML and ALL, two very different types of leukemia and these are still uniformly treated together because we haven't yet developed therapies that differentiate the two. Therapy specific for ABC large cell or therapy specific for GCB large cell lymphoma and as a result because we treat them the same they are really not diagnosed as separate diseases even though biologically they appear to be quite different.

Lisa Garvin: Are there any biomarkers that have been identified for this type of lymphoma?

Dr. Jason Westin:  Yes, so the way that we initially found that there are multiple subtypes of large cell lymphoma was using a technique called gene expression profiling, this is basically taking a tissue from the abnormal cells and looking at the genes that are expressed and we found that there is a certain we call them signatures that seem to correlate to different types. We can cluster these diseases into really three main categories, so these biomarkers are mainly used for research right now but could eventually be used for therapy. I mentioned three categories, the two I've mentioned previously the ABC subtype and the GCB subtype are relatively similar to each other. They do have significant differences as I mentioned before but the treatment for those really is not advanced beyond R-CHOP. A third subtype called primary mediastinal large B cell lymphoma has very recently had a dramatic advance in its therapy and now R-CHOP an inferior front line therapy and should not be used for patients. There's a paper recently from Dunleavey [phonetic], et al in New England Journal that showed that a combination called R-EPOC had extremely good efficacy and prevented the need for radiation therapy. Patients had incredible outcomes at 5 plus years, so in terms of biomarkers there are ways to differentiate this primary mediastinal subtype from the others. Gene expression profiling is something we've used to differentiate those but it has not yet reached clinical practice.

Lisa Garvin:  Now you said that CHOP the standard regime has been around for about 30 close to 40 years.

Dr. Jason Westin:  Um, hum.

Lisa Garvin:  What has happened in recent years to kind of move away from that standard treatment?

Dr. Jason Westin:  That's a great question, that's a research focus of mine on how to move beyond CHOP. In the mid 90's, in the early 90's there was a large paper in the New England Journal that looked at four different regimes, four different similar regimes to CHOP to try and see if there was any one that could be better or superior or have different characteristics that could say we could use that instead of CHOP and basically found in this paper that all four regimes had about the same efficacy but CHOP was less toxic and therefore CHOP has remained the gold standard since that time and that paper came out 20 years ago. So now what's done instead of moving beyond CHOP we're trying to do things different than CHOP is basically adding drugs to CHOP so a new drug will be added and if we do a randomized trial it will be R-CHOP versus R-CHOP plus the new drug so there's not been a lot of innovation yet to change that but there's not been a lot of innovation yet in terms of moving to novel, less toxic more targeted therapy in the front line setting.

Lisa Garvin: Let's talk about the overall prognosis for diffuse large B cell lymphoma patients is this a disease that is chronic in that they may be living with these symptoms for the rest of their life and also is there a fear of recurrence?

Dr. Jason Westin: That's a good question so this is not something people live with long term, either it's eradicated or survival is short. So this is an aggressive disease and people get urgent therapy up front we start chemotherapy relatively soon after diagnosis and people generally get six cycles of therapy and if they go into remission the hope and expectation is the disease will not come back but relapse is always a possibility. Generally the first two years are the higher risk time when the disease could come back. If the disease comes back we cannot go back to standard initial therapy because the disease is generally thought to be resistant to that therapy and survived it the first time so going back to the well a second time will result in toxicity but not really good efficacy, that's a bad trade off. Generally if the disease comes back people who are fit and don't have significant medical comorbidities will get aggressive chemotherapy followed by a treatment called an autologous stem cell transplant and of 100 patients that have relapse diffuse large B cell lymphoma only about 50 percent will be eligible for stem cell transplant and the 50 who are not invariably will ultimately die of their disease. The fifty who were eligible will get this aggressive salvage chemotherapy and about half...somewhere in the neighborhood of half the patients will respond to that aggressive therapy, the ones who don't respond to the aggressive salvage chemotherapy will ultimately die of their disease. Those that respond go on to transplant and about a third of patient who go on to transplant are long term survivors. So we're right now curing somewhere in the neighborhood of 10 to 20 percent of people with relapse large cell lymphoma. So if the disease comes back it's not something you live with long term its something that you either survive from an aggressive therapy like a transplant or you ultimately die of the disease.

Lisa Garvin:  Okay and I didn't touch on basics at the beginning of the podcast but this is obviously a disease kind of the middle age right, you're usually in your 40's, 50's, 60's?

Dr. Jason Westin:  Yeah it's generally in that age range, we see all ranges so it's young patients for the primary mediastinal subtype, it's generally younger patients but for the ABC subtype and the GCB subtype generally in the 40's to 60's range.

Lisa Garvin:  And let's also touch on the symptoms; I know that the symptoms can sometimes be vague.

Dr. Jason Westin: Yes, so lymphomas in general have sort of a variety presenting symptoms and the most common is that somebody feels a lump, so they are in the shower and they notice something under their arm or in their groin or in their neck, feels enlarged and they present to their doctor that way. But people can also have a variety of nonspecific symptoms, so people can have fevers, night sweats where they actually soak the bed clothes, significant night sweats, weight loss, itching things that aren't something you can say definitively if you have a symptom like that, that you have lymphoma but something is wrong type symptoms and often times that's the way people are presenting having a nonspecific symptoms that their doctor works up and finds a mass.

Lisa Garvin:  Do primary care providers know what they're looking at because obviously they'll take a blood test but would they know what they're looking at in a primary setting?

Dr. Jason Westin:  I'm not sure, that's...it's something that would be diagnosed because this is something that generally progresses fairly rapidly so somebody didn't know what they were looking at pretty soon it would declare itself and something would need to be done in terms of a workup so this wouldn't be something that would be missed on a chest x-ray and not found ever. This would be something that if a symptom presented and it wasn't worked up immediately, pretty soon the patient would represent and would require workup so I don't think that necessarily someone would give the diagnosis immediately I think that very soon thereafter the patient would show up again and say we need to continue looking into what this is.

Lisa Garvin: And it's very important for lymphomas in particular because there’s so many different subtypes an accurate diagnosis are crucial.

Dr. Jason Westin:  That's exactly right the treatment for different types of lymphoma depends on the diagnosis so a qualified hematic pathologist looking at a biopsy is required because low-grade lymphomas as treated in one way, higher-grade lymphomas are treated completely different way and having the wrong diagnosis in the beginning can have a significant down stream effect.

Lisa Garvin:  Do you have any final thoughts Dr. Westin?

Dr. Jason Westin: I think this is a very common disease and it's one that we are using therapies that are very old and have not yet incorporated our dramatic advances over the past ten years and I think the only way we can incorporate advances like that is by having patients go on clinical trials. Having the majority of patient in the United States treated off clinical trials does not allow us to really advance and learn and move beyond a treatment that was developed in the 1970's. Most people wouldn't buy a car or phone to TV from 1970's, to have a therapy for a fatal disease that is that old doesn't make a whole lot of sense. So I think until we develop nontoxic, targeted therapies which are highly effective I think clinical trials are a must and should be considered for every patient.

Lisa Garvin: Thank you. If you have questions about anything you've heard today on Cancer News Line, contact ask MD Anderson at 1 877 MDA-6789 or on line at mdanderson dot org slash ask. Thank you for listening to this episode of Cancer News Line, tune in for the next podcast in our series.