Hodgkin's Lymphoma
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
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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