>> Welcome to Facebook Live,
I'm Elizabeth Tracy.
So privileged to be here in the
Johns Hopkins Children's Center
with Doctor Patrick Brown,
a childhood leukemia expert
and Amanda Leinenger,
our social media guru.
Today we're talking about a really revolutionary
new treatment for leukemia
Now I'm going to let you serve that up.
>> Alright, great.
Thanks Elizabeth, thanks Amanda.
So the new treatment that we're talking about today,
it's got a couple of different names.
The easiest one to pronounce is Kymriah.
It's also got a generic name,
which is tisagenlecleucel,
so Kymriah we'll go with. >> That's really good.
>> Thank you, thank you.
I've been practicing.
And so this is a new treatment for children
and young adults that have a form
of leukemia called B-cell ALL,
which stands for acute lymphoblastic leukemia.
And it's specifically for patients
who either are not responding at all
to standard chemotherapy or have relapsed
for a second or greater time
after they've received chemotherapy.
And so this is a new treatment
that we have in our toolbox
to treat patients in that situation.
>> Help me understand why it's so revolutionary.
>> There's a few different reasons.
The reason the name is so long is the name has
to capture all the different kind of novel elements of it
and one of them is that it's the first genetic therapy.
And I'll explain what that means in a moment,
that's been FDA approved.
The second is that it's a cellular therapy.
So it's not a drug, per say.
It's not a chemical.
It's actually using human cells as a treatment for a disease
and those are both very novel things.
The third thing that makes it so novel is
how effective it is against a disease in a situation
that before now,
we've had no effective therapies for.
So, our standard treatments for leukemia,
which include different forms of chemotherapy
and sometimes radiation therapy,
are completely ineffective against the particular situation
that this therapy was developed for
and its success in treating that
and the responses that we've seen in that situation
are novel and unprecedented.
And that's why there's so much excitement about it.
>> My understanding is that someone's own cells are taken
and then they're modified and then given back.
This has been a goal that's been advocated for
or pushed for for years in medicine.
>> Absolutely.
So, I remember in medical school,
which unfortunately was a very long time ago for me,
learning about the promise of immunotherapy
and the idea that we could harness the power
of our immune system.
And it really is so powerful to help treat diseases
and specifically in cancer.
I think that's where the promise
of immunotherapy was really,
generated the most excitement.
And to see it finally come to fruition after all
that time is very gratifying.
Mostly because it gives our patients hope
where in the past we haven't had something
to give them that hope,
treatments that worked in that situation.
>> There are some side effects,
however with this treatment.
>> Absolutely. Absolutely.
So to understand the side effects,
I think it's important to understand how it works.
So why don't we spend a few minutes talking about that?
As I mentioned,
our immune system is a really incredible
orchestrated system that's designed to protect us
from many different things in our environment
that can be harmful.
And the way I like to think about the immune system is
that it's a group of security guards,
each of which has been trained to recognize a threat.
So literally,
the main component of our immune system that's relevant
for this discussion is T lymphocytes.
It's a type of white blood cell
and it's called a T-cell or a T lymphocyte.
The way T lymphocytes are set up is
that there's literally about 100,000 different groups
of T-cells in our body and we all have them.
And each little group is trained
to recognize something as foreign, usually infections.
And any cell in the body,
or any part of the body that has that threat is eliminated
or killed by those cells.
So, they're very focused security guards,
each of which has their own mission, if you will.
For example, if I was infected with the flu virus
and it is the flu season so go get your flu shots,
had to get that in there.
So, if I was infected with the flu virus,
there's a group of T-cells in my body
that is trained and ready for the flu virus
and attacks the flu when it enters my body
and keeps me alive.
That's how the immune system works.
And the immune system again,
is set up to handle just about any threat
that can come our way when it's healthy.
The way this system works, this treatment,
is that we harvest from the patient their own normal T-cells
and that includes not only the T-cells
that are trained to fight the flu,
but also a group of T-cells that's trained
to fight everything else.
So it's a big mix of T-cells.
And we then, and by we,
I mean scientists and laboratory technicians,
not me personally,
but the techniques have been developed
to put a new gene into those T-cells
that basically retrain them
to all recognize the same thing, the same threat.
And that threat is a protein that's on the leukemia.
And so once those cells have been retrained genetically,
in order to recognize a protein that's on the surface
of the leukemia cells,
in this case the leukemia is a B-cell leukemia,
which is another form of white blood cell,
then they're given back
to the patient in a simple IV infusion,
like a transfusion or any IV infusion
and those cells are retrained.
They see the leukemia as a threat
and just like the patient had a flu,
they go and kill those cells.
Now we get to the side effects.
The side effects are basically the same you would get
with a very severe flu infection.
Because when T-cells kill,
when those trained T-cells go and kill that leukemia,
they release chemicals called cytokines
that make us feel the symptoms.
Fever, they can lower blood pressure.
it can make you very, very sick in the short term,
just like the flu can.
But once the leukemia has been eliminated,
just like once an infection has been eliminated,
the body can recover and heal
and get back to its normal state.
So the most severe side effects,
the most dangerous ones,
are in that initial period when those
retrained T-cells start to expand
and circulate in the patient,
find their target,
and start to kill them.
And it releases those chemicals that are necessary
for them to do their job,
but they do cause side effects and symptoms.
So fever, low blood pressure,
difficulty handling fluids,
and it can be very, very severe
to the point where some patients,
it can be even life threatening.
That's why it's very important for patients
to be treated in centers that have expertise
and can handle these side effects.
>> Like this one.
>> We actually have a question from one of our viewers.
Will this be the new standard of care for patients with ALL
or only for those who have relapsed?
>> It's such a great question, Amanda.
As of right now,
this is a treatment option
for the situation that I laid out.
Children and young adults
that have this form of leukemia,
B-cell lymphoblastic leukemia,
that has not responded
or has come back at least twice after standard treatment.
Now we as a group, as a field,
are conducting clinical trials and other studies
to figure out whether this treatment could
or should be introduced earlier in the disease process so
that it could become standard therapy even in situations
that are earlier in the disease process, if you will,
maybe to prevent relapse, for example.
So it's not standard yet.
It is a treatment option and a standard therapy
for the specific indications that I've talked about,
but we are hopeful that we could potentially figure out
how to use this therapy earlier on
to prevent relapses and perhaps treat patients
more effectively than we currently can
with fewer side effects overall.
The other thing I should mention about side effects is the
protein that these retrained security guards can recognize
and kill on the leukemia is a protein called CD19
and it is expressed not only in the leukemia cells,
but also on our normal B-cells.
So this form of leukemia arises from our normal B-cells
and shares with it that CD19.
So another side effect is
that the treatment also eliminates our normal B-cells,
another component of our immune system.
Fortunately, we can survive without normal B-cells
by replacing what normal B-cells are designed to produce,
which are immunoglobulins, or antibodies.
So patients that receive this therapy,
their B-cells are also eliminated
and they have to come in once a month
or there's forms that you can get less frequently
or more frequently than that,
that can replace the antibodies
that the B-cells normally produce.
So those are the major side effects.
>> And you anticipate
that this antibody replacement is something
that would have to take place throughout the lifetime.
>> That's a great question.
One of the unanswered questions is
how long do the CAR T cells persist
and remain active in the patients
after they've been infused?
And the answer is it depends.
For some patients,
the lifespan, if you will,
of the CAR T cells has been shorter
and for other patients,
there are patients that where it so far,
has been indefinite.
Where they've gone for years
and their CAR T cells are still there,
still doing their job.
For those patients,
certainly they would continue to have
to get the antibodies to replace that.
What we know about the persistence
of the CAR T cells is that there's a link between
that persistence and whether the leukemia stays away or not.
And so in one way,
that persistence is something that we want to see
because that would be correlated
with long-term leukemia control
and perhaps even cure,
although we're not quite certain of that yet.
We need time to figure that part out.
The downside of persistence, of course,
is that the B-cells are continuing to be eliminated
and need to be replaced.
So one of the ways
that this therapy could potentially be improved
is if we knew when the CAR T cells were no longer needed.
In other words,
the security guards have done their job,
they've killed all the leukemia
and the only thing they're doing now
is killing innocent bystanders,
then could we potentially turn that off?
And so there is some research being done
to potentially engineer in
a suicide mechanism, if you will,
to tell the security guards they can retire.
So those are the sorts
of improvements in the next generation of this therapy
that could potentially make it
even more effective than it is right now.
>> You used a term that I don't think we've defined yet
and that was CAR T cells.
>> Ah, yes.
So, CAR T cells.
CAR is an acronym
and it stands for chimeric antigen receptor.
The way T-cells recognize their target is
with an antigen receptor.
So when we take a T-cell
that is normally looking for the flu
and we tell it to look for CD19 instead,
that's a chimera.
We've forced it to do something it's not normally doing
through engineering.
That's a chimeric antigen receptor T-cell.
CAR T-cell.
That's the shorthand for these types of therapy.
Kymriah is one example and the first example
of an FDA approved CAR T-cell product.
But that's what CAR T-cell means.
Thanks for pointing that out.
>> How optimistic are you
that this strategy will also be useful
in other childhood leukemias
and then other types of tumors in children
and in adults, for that matter?
>> That's a great question.
The history of treatments for any disease
and in particular, for cancer,
is such that the easiest subset of the disease to treat
with that therapy is the first that it's effective in.
And the reason why B-cell leukemia was the first
that this worked in is
because we can get away with not having normal B-cells.
The challenge of applying this therapy to other forms
of leukemia and other forms of cancer is that
for most other types of leukemia and cancer,
if you eliminate the normal counterpart of what
that cancer arose from,
then that would lead to unacceptable side effects.
So in this case,
we can replace B-cell function with immunoglobulin.
For example, there are leukemias that arise from T-cells.
You can imagine if you eliminate all normal T-cells,
in addition to the leukemia T-cells,
you've got a problem
because you can no longer fight off infections, for example.
Same thing with what are called myeloid leukemias, or AML.
If you eliminate the normal counterparts of those cells,
you can't make key components of blood
and that's a difficult situation to arise from.
It's true of solid tumors as well.
Now, am I optimistic
that those challenges are going to be overcome?
Absolutely, just like the challenges overcome
to make this therapy available for B-cell leukemia,
there is the expertise,
intelligence, drive, motivation
to overcome those challenges
and make this therapy and other immunotherapies applicable
for a broader range of patients.
It's just a matter of time.
>> You sound like you're really excited about it.
>> This is the most exciting time
that I have certainly experienced in my field.
We have had an explosion of new, effective,
and targeted therapies for cancer
and specifically for childhood leukemia.
And I can't imagine a more exciting time for our field
and the most gratifying part of that is that you can start
to see a day when many of these cancers become,
if not completely curable,
if not completely eliminated, I should say,
curable in every case and with limited,
if any long-term side effects.
And that is an exciting thing to see.
And it's just so cool
that it's harnessing something naturally within our bodies
that's just this powerful natural force
and harnessing it and directing it
to do good and eliminate disease.
>> On that wonderful, optimistic note,
is there anything else you'd like to add?
>> No.
>> That'll do it?
>> Get your flu shots, I guess.
>> (laughs) Okay, thank you so very much
for joining us today on Facebook Live.
I'm Elizabeth Tracy,
we're here at the Johns Hopkins Children Center.
Patrick Brown,
thank you so very much for joining us.
And Amanda,
thanks for your expertise with the social media.