Hodgkin's Lymphoma

M. D. Anderson Cancer Center

Cancer Newsline Audio Podcast Series

Date: July 13, 2009

Duration: 0 / 11:57

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Lisa Garvin:

 

Welcome to Cancer Newsline, a weekly 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 we're talking with Doctor Anas Younes, he's the Director of Clinical and Translational Research in the Department of Lymphoma and Myeloma here at M. D. Anderson. Welcome Doctor Younes. There's a lot of exciting stuff going on I understand for Hodgkin's Lymphoma, and we're gonna talk about standard therapies and emerging therapies for Hodgkin's Lymphoma. First of all let's talk about Hodgkin's Lymphoma itself. What is the, the general population and what are their treatment options as of today?

 

Anas Younes, M.D:

 

So Hodgkin lymphoma is grouped into two major groups, one is called classical Hodgkin lymphoma, which is the most common type in North America, accounts for about 8,500 cases per year. And the second type, which is a rare type, it's called lymphocyte  predominant Hodgkin lymphoma, which is, which is about 1,000 cases probably per year. So what we will focus today is mainly on the classical Hodgkin lymphoma. So if you take 100 patients with current treatments you can cure about 70, 75. So the cure rate is 70 to 75%, which is very good compared to other cancers. And, and the cure rate when we talk about cure, even in the worst case scenario, patients will have advanced phase, which lung, bone marrow, liver disease, still can be curable, which is not common for other malignancies. So it's a highly curable disease.

 

Garvin:

 

And isn't it true that you have aggressive and slow growing, or indolent lymphoma's?

 

Younes:

 

For Hodgkin we don't talk about aggressive or indolent, this is more applicable to non-Hodgkin lymphoma. For Hodgkin lymphoma we talk about poor prognostic type, and favorable progressive type. So there's, so, so, advanced stage classical Hodgkin’s lymphoma can have good, good features or bad features.

 

Garvin:

 

And lymphoma, or Hodgkin's lymphoma tends to strike a younger patient population than many other cancers.

 

Younes:

 

That is correct. So the median age, or the average age of patients with Hodgkin lymphoma is in the 30's, 31, 32, compared to the non-Hodgkin lymphomas, where as it  is in the upper 50's and 60's.

 

Garvin:

 

Tell me about the frontline treatments that are available today here at M. D. Anderson for Hodgkin's lymphoma.

 

Younes:

 

So although the cure rate for Hodgkin lymphoma is a very successful story, the current treatment that we use to maintain this high cure rate was produced in the 70's. So we haven't made any major progress in the cure rate for almost 3 decades. It works, so we're not, we're not complaining here, but a 70% cure rate, or 75% cure rate for, for patients who are in the mid 30's is not, not good enough. And then if you look at the average lost years from productive life, every time you lose 1 patient it's tremendous. So think back tremendous on, on, on life. So would like to see 100% cured. And then there, there's different ways of, of approaching this of course.

 

Garvin:

 

And since it's a, a disease of the blood and the lymph system, we're not talking about surgery. I mean these are mainly chemotherapy type therapies.

 

Younes:

 

That is correct. So a lymphoma in general, or we don't think of it as cured with surgery. We use surgery for palliative, to relieve symptoms, or for diagnosis. Surgery is not considered the primary treatment modality.

 

Lisa:

 

And what are some of the frontline treatments that are producing success stories today?

 

Younes:

 

So the most widely, there's different regimens, but the most widely used regimen these days for the treatment and cure of patients Hodgkin lymphoma, it's called ABVD, it's a four drug regimen. Adriamycin, Bleomycin, Vinblastine, and DTIC, or Dacarbazine. And this 4 drug regimen I've said was introduced in the 70's. And it, works. The average patient with advance stage will require 6 months of therapy, and patients with less advance stage, or early stage, the average person will acquire about 4 months of therapy, plus minus radiation therapy.

 

Lisa:

 

Now you were talking about transplants. How many lymphoma patients do undergo a stem cell transplant?

 

Younes:

 

So if we're talking about Hodgkin lymphoma, the standard of care for patients with Hodgkin lymphoma will relapse, or don't respond to frontline regimen. It gives them a second line regimen of what we call salvage regimen. And patients will respond to the salvage regimen. Then they will be offered stem cell transplantation. And the majority of cases for Hodgkin lymphoma would be autologous stem cell transplants. So we'd like to see every person who doesn't respond or fail after frontline therapy undergo stem cell transplantation for Hodgkin's lymphoma.

 

Garvin:

 

And by autologous you mean that their own stem cells.

 

Younes:

 

That is correct. So you take the stem cells from the prefer blood and give it back up to the high dose chemotherapy. And if you just approach, give salvage therapy, lose response, and give stem cell transplant, you could cure on the average of about 50 to 60% of the patients. Which is not bad for a second chance.

 

Lisa:

 

And what is happening in the pre-transplant and the transplant population for Hodgkin's lymphoma, new treatments for them?

 

Younes:

 

So the, again, same story. The regimen that we use in pre-transplant settings, the most widely used regimen is called ICE and there's variations on what we call platinum based regiments. So there's ICE DAP, ESHAP and ASHAP.

 

Most of these regimes were introduced 20, 25 years ago at least. And that's the main, main regime that we use in a pre-transplant setting.

 

Lisa:

 

So what are some of the new treatments that are available for people in the pre-transplant setting?

 

Younes:

 

Right, so, so I'd like to break this down to the frontline regimen and then pre-transplant  regimens, because it makes a big difference. So the frontline regimen, as I said the ABVD's been there for almost 3 decades. And then there's different ways of trying to improve the outcome in patients with frontline, with untreated patient Hodgkin lymphoma. What we're doing here is we're combining an antibody that was originally proved for patients with non Hodgkin lymphoma, B cell Hodgkin lymphoma, called Rituximab. We're combining it with ABZD. And based on at least a, a large phase 2 data from here, it seems that it is better than ABZD. In a non, non-randomized fashion. So what we're doing right now, we have randomized trial, multi-symptom randomized trial, comparing ABVD with Rituximab plus ABVD hoping that this will improve in the cure rate with ABVD alone. That's for advanced stage. For early stage Hodgkin lymphoma we are also using the similar approach, but comparing what would be considered as a standard of care, which is ABVD for 4 cycles, plus radiation therapy. We're comparing it with ABVD for 4 cycles. But with Rituximab with no radiation therapy. With the idea that radiation therapy may induce sometimes side affects, and if we can eliminate therapy by substituting it to with Rituximab, we may be able to improve the cure rate.

 

Garvin:

 

 And Rituximab is a monoclonal antibody?

 

Younes:

 

That is correct.

 

Garvin:

 

Explain how that works.

 

Younes:

 

So Rituximab targets a protein or antigen on the surface of B lymphocytes. The cancerous B -lymphocytes, and the normal B lymphocyte. So obviously it was originally designated to kill cancerous B lymphocytes, or B cell non-Hodgkin lymphoma. The, in Hodgkin lymphoma the way we're using it is to target the reactive lung cancer, B lymphocyte in the micro environment. So we think that if you deplete reactive B lymphocytes in the micro environment. You can deprive the cancer cells some important support and growth factors, and will make the cancer cells more susceptible to chemotherapy.

 

Garvin:

 

 Is this what we're calling targeted therapy or personalized medicine?

 

Younes:

 

It's a, it's in a way targeted therapy. It's not, I wouldn't call it as personalized therapy yet, because if the same approach given to all patients, so it's not tailored per patient. So it's using the same approach. But the future, hopefully we will be able to predict who may benefit from this, and who may not benefit from this. And that will be called personalized cancer therapy.

 

Garvin:

 

Aren't' there several receptor proteins that you're looking at in Hodgkin lymphoma?

 

Younes:

 

That is correct. So that's, that's, again our receptor proteins on the cancerous cells of Hodgkin lymphoma, which is reed cir mvec cells. So these are in, in early development, and different antibodies from Rituximab that target different antigens, and primarily targets antigen called CD30. So these are undergoing testing in phase one and phase two setting. And of course, transplant patients, which is, which is an unmet need population that can benefit with these experimental approaches.

 

Garvin:

 

And it looks like, I'm not sure if it was CD30 in particular, but it looked like you had some promising phase two results, oh, that's actually TRAIL that I'm talking about.

 

Younes:

 

That's no, no, actually so, so there's several agents in either antibodies or small molecules that are currently being evaluated for the treatment of Hodgkin lymphoma. And I've said when you try a new agent, ethically because it's a highly curable disease. You have to test it in non-curable patient's, which is by default, patients who relapse after antilogous transplant. So we have several agents that are currently being tested. But the leading compounds that are, seems to be promising are, one called SGN 35, which targets CD30 antigen. But it's not a naked antibody like Rituximab, it's conjugated. So it's a, it's a, it's a antibody drug conjugate. The anti body is conjugated to a chemical or toxin. And go, find it to myself sick to, internalize, and deliver the toxin inside the cells and kill it. So this is more of a targeted therapy. And the second promising air, agent, falls into the class of HDAC inhibitors, or Histone deacetylase inhibitors. And the leading compound right now, it's called Panobinostat, which is oral compound. You take it Monday, Wednesday, Friday. And then, and, and till we see responses.

 

Garvin:

 

Tell me about the post transplant. People who have relapse post transplant, very few options, if any, available?

 

Younes:

 

So, yes. So when patients relapse from autologous transplant, we don't think of it as, as curable anymore. The average, if you take your 100 patients relapse from an autologous  transplant, the average lifespan is about 2.5 years. And again, for patients who are in their 30's, it's, it's, it's a, it's not acceptable, I think. And that's why we're testing a lot of new agents in this patient population. Speed up the screening process. And once we find or identify a potentially second drug, we move it in upfront or in, in combination pre-transplant settings.

 

Lisa:

 

Anything that's about to move into phase 3 for the post transplant population?

 

Younes:

 

So the SGN35 is right now in what we call pivotal trials. So the FDA agreed, because an unmet need. And not to waste long time in a randomized trial. They would approve a drug based on, good response rate, in a, in a large number of patients, which is defined as about 100 patients. And in a phase 2. Same thing for Panobinostat in a potentially pivotal trial, so the drug can be potentially approved based on the solid data from a phase 2 trial.

 

Garvin:

 

Sounds like there's a lot of things on the horizon for Hodgkin's lymphoma. Do you have any final thoughts Doctor Younes?

 

Younes:

 

Well my, my only hope that again there is many compounds available, many of them are promising agents. My only hope that patients would participate in clinical trials as much as they can. So the fact that we can complete these trials, the better for everyone, including the patients.

 

Garvin:

 

Great. Thank you very much. And for those of you listening, if you go to www.clinicaltrials.org and type in lymphoma, you can find some of the trials that are available here at M. D. Anderson. If you have questions about anything you've heard today on Cancer Newsline, contact AskMD 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 next week for the next podcast in our series.

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