(ambient synthesizer music)
>> I think there's really two main reasons
why there's so much excitement for CAR T-cells,
and the first is that for literally decades,
developing immune therapy has been considered
the Holy Grail of cancer therapeutics.
It's something that I remember being taught
back in medical school had the power
to really change the landscape of cancer therapy.
CAR T-cells are the culmination
of that 30 years or so of research,
and to see it come to fruition and be available for patients
is really a huge advance.
The second reason is because of the results,
so in the diseases that we're using it for,
and primarily in the disease
that I'm most interested in which is childhood ALL,
the response rates where 90% of patients
go into a deep remission and potentially 60% of patients
can be cured with this therapy,
is just amazing given the fact that those patients
were simply out of standard options
before this therapy came along.
At this point, there's two main groups of patients
that are candidates for CAR T-cells.
One are children and young adults with B lineage ALL,
and the other are adults
with an aggressive form of B lineage lymphoma,
and as it stands now patients with both of these diseases
are eligible only if they've failed up-front therapy,
if their disease has relapsed
or it hasn't responded to up-front therapy.
So the process starts by identifying an appropriate patient
for the therapy, and then the first step
in the management of the patient is to have them
come to Johns Hopkins to undergo what's called apheresis,
and that's where we collect the patient's own T-cells.
At that point, those T-cells
are shipped off to the manufacturing facility
to create the CAR T-cell product.
That takes anywhere from three to four weeks on average,
and during that time, we typically
will have the patient receive bridging therapy,
and that's therapy designed to keep their leukemia
or lymphoma kind of at bay if you will
before their CAR T-cell product is ready for us to infuse.
We receive the product back from the manufacturing facility,
and it comes back cryopreserved or frozen,
and then we bring it to the patient's bedside, thaw it,
and infuse the product at that point.
The four or five days before we infuse the product
we give the patient
a little bit of conditioning chemotherapy
to make the patient's body
ready to receive the T-cells if you will,
and then we follow the patient very closely
for the next month
which is when the first evaluation occurs.
The process is very much a collaboration
between the referring hospital
or physician and Johns Hopkins.
Really the only two parts of that process
where the patient really needs to be at Johns Hopkins
or in the immediate vicinity are the one to two days
required to collect the T-cells,
and then the probably four to five weeks
that span the actual infusion of the CAR T-cells.
The remainder of the time we can work with the local
referring physician and hospital
to provide therapy for the patient
and follow up after they receive their CAR T-cells.
The two main risks of CAR T-cells
are a condition called Cytokine Release Syndrome
or CRS, and neurotoxicity.
The timing of these two side effects is different.
The Cytokine Release Syndrome, the risk for that
is really anytime from about one day
after the CAR T-cells are infused to about a week after,
so in that first week after receiving the therapy,
and the neurotoxicity the timing is a little bit later.
It can be as long as a few weeks after or even longer
after receiving the CAR T-cells.
The Cytokine Release Syndrome is due to the activation
of the patient's T-cells
after they're given back to the patient.
What happens there is the T-cells when they get activated
release chemicals called cytokines
and those cytokines cause symptoms like fever,
low blood pressure, difficulty breathing,
difficulty handling fluid
and fluid leaking basically in the body,
and that's the Cytokine Release Syndrome side effect.
The neurotoxicity is probably also caused
by the release of cytokines, but it occurs later
and it affects the function of the brain,
and the two main side effects that one can see
are what we call encephalopathic symptoms
and these would be things like confusion,
not being able to speak properly,
and then the other is seizures,
so we give seizure preventative medications.
Fortunately, both Cytokine Release Syndrome
and neurotoxicity are in virtually all cases 100% reversible
and patients go back to their baseline
after they've received that.
Now this is a distinct pattern of toxicity
compared to the alternative treatments in this situation
like intensive chemotherapy or transplant.
So the Cytokine Release Syndrome, neurotoxicity are unique.
They occur relatively early and they fully resolve,
whereas chemotherapy and transplant
can have prolonged side effects, and so we really think
there may be an advantage to CAR T-cells in that way.
And then the final thing to mention
is that CAR T-cells will eliminate normal B-cells
as well as tumor B-cells,
and so patients can be left without B-cells
for a long period of time.
That's called B-cell aplasia,
and that can require immunoglobulin infusions
for potentially life after patients receive this therapy.
Unfortunately, no.
Like most therapies or all therapies to date,
they don't work in every patient,
and there's two main reasons
why CAR T-cells currently are not working.
For about 10% of patients,
the T-cells simply don't expand and don't engraft
in the patient after they're infused,
and then in another 30% of patients,
they engraft and the patient responds,
but then some period of time later
usually within several months,
the patient's leukemia comes back usually
because it has learned and adapted
and now no longer expresses the protein
that the CAR T-cells are targeted
against which is called CD19.
That's called CD19 escape when that happens.
So there's lots of work going on to optimize
the CAR T-cells to reduce both of those reasons
that they don't work,
to both reduce the rate of patients
whose CAR T-cells don't engraft after they're infused
from 10% down hopefully to 0%,
and also to modify the CAR T-cells
so that they can target
more than one protein on the leukemia
to prevent that CD19 escape that's occurring.
They're very expensive.
The current price tag for the CAR T-cell products
are anywhere from 350,000
to almost $500,000 for the treatment.
So far insurance companies
have been reimbursing for the cost of the CAR T-cells,
and have been covering the CAR T-cell cost
at least for the patients that are being treated
in accordance with the FDA indications.
The companies have also set up programs
to help make sure that the treatment is affordable
to as many patients as possible,
so there are things like
copayment, co-insurance payments and reimbursements,
there's reimbursements for lodging and travel
associated with having to go
to a different center for CAR T-cells,
and there are programs where the CAR T-cells are provided
free of charge for patients that are indigent or uninsured.
Hopefully most patients can find a way
to make these products affordable over time,
but it's a concern moving forward that with therapies
this expensive that the system will be able to sustain
providing them for patients.
So we are one of approximately 40 or so centers
that are able to offer this treatment
to children and young adults.
In our area,
we're one of the only programs in the Mid-Atlantic.
There's, in Philadelphia is
the Children's Hospital of Philadelphia program.
There's us and then I think the next one
to the south of us is Duke,
and then there's a couple to the west
out once you get to the Midwest,
so we cover a pretty large region of the United States
and are taking referrals from that area.
The other thing is our children's center I think
is one of the top children's centers
for all of the different services that it takes
to make CAR T-cells a reality, so you have to have
a very high functioning intensive care unit,
cell therapy laboratory, the ability to do pheresis on site,
physicians that are used to taking care
of very sick patients with cellular therapy,
and we have one of the best
bone marrow transplant programs here,
and we all work very closely and coordinate very closely
to make sure the patient gets the very best care.
So we're certainly not the only center
that does CAR T-cells, but I'd like to think
we're one of the best, and I hope that patients
will feel that way when they come here for treatment.
(ambient synthesizer music)
(children laughing)