I am Dr. Alaa Ali, I'm a Hematologist Oncologist at the
transplant and immunotherapy program at MedStar Georgetown
University Hospital. So I see patients with a variety of blood
and bone marrow cancers that require either autologous stem
cell transplant allogeneic stem cell transplant or car T-cell
therapy. My philosophy for patient care is that since we
treat patients with highly aggressive types of
cancers that oftentimes have failed other forms of therapies
such as chemotherapy, targeted therapy or radiation therapy,
we're really here committed to bringing to this group of highly
complicated patients and diseases cutting edge therapies
that could be highly effective and sometimes even curative. So
we are committed at the transplant program to first help
those patients make the right decision about the treatment
that they need, but also navigate them through the
process, which can be a little bit overwhelming, since
those treatments are highly complicated, but we try to make
the process as smooth as possible. Immunotherapies and
CAR T-cell therapy and cell therapies in general are
ushering in a new era in medicine in which not only do we
have effective treatments to offer those patients with highly
aggressive and sometimes life threatening cancers, but also
these treatments are effective and sometimes even curative. So
when I was at the phase of my training, trying to figure out
the kind of medicine that I would like to practice, cellular
therapies immunotherapies, car T-cell therapy, and oncology in
general seemed the most exciting and the most likely to allow me
to have an impact on patients lives and, and help patients in
general. So on the other hand, because those treatments are
relatively new therapies, there is a big room for scientific and
clinical research, to try to refine those treatments, make
them even more effective, overcome some of the challenges
that they sometimes pose. So, the field was very exciting to me
from all aspects. Well, I think there's no doubt that the most
exciting aspect of what we do, not just me, but probably every
physician who practices what I practice is the ability to offer
patients with life threatening cancers, highly aggressive
cancers, some effective and even curative therapies. So we're
allowing those patients to actually see the light at the
end of the tunnel. And it's extremely gratifying too. Goes a
long way and keeps you going. So again, there is a lot of
enthusiasm about immunotherapies and car T-cell and cell
therapies in general. So, scientists and clinicians and
researchers are trying to bring those therapies to a broader
spectrum of diseases and patients and make them even more
effective, overcome some of the resistance mechanisms by which
cell therapies try to, or cancer cells try to
outsmart the therapies that we offer, and minimize the side
effects as much as possible. So the ultimate goal is to push
the field forward and try to cure as many patients and
diseases as possible. MedStar Georgetown and Lombardi
Georgetown Cancer Center as well as John Theurer Cancer Center in
New Jersey constitute a consortium that is designated by
the National Cancer Institute, or the NCI, as Comprehensive Cancer
Center, which is the highest federal rating that any
cancer center can achieve. And what that means is that we
meet the standards and the criteria of the NCI not just for
clinical services and being able to offer patients cutting edge
therapies, but also cancer research. There are only about
70 cancer centers in the United States and Georgetown Lombardi
Cancer Center is the only one in the District of Columbia. So how
does that translate in terms of patient care? And why does it
matter to patients?
I think it matters because if you are a cancer patient and you
are treated at comprehensive cancer centers like ours, you
will have access to exceptional patient care, innovative cancer
research as well as advanced technology. And one of the
themes that is common in comprehensive cancer centers
like ours is that physicians are usually highly specialized,
which allow them to become experts in their field. So for
example, at the same time they perform like one team. So, for
example here, at our center, we meet multiple times every week
to discuss all the cases that come out or we encounter in the
clinic and try to come up with individual treatment plans for
each of those patients. So, you have the lymphoma specialists,
you have the Leukemia specialists, you have the
multiple myeloma specialist and the transplant physician trying
to discuss all these cases and formulate the most appropriate
plan for each of those patients. So cancer medicine has become
highly complicated that this is probably the only effective way
to actually treat such a complicated disease like cancer
when the science is advancing so fast.
So car T
cell therapy is a form of immunotherapy in which we use
the patient's own immune system or we harness the patient's own
immune system to fight cancer. It's also considered a form of
cell based therapy in which we use the patient's immune cells,
or we retrieve the patient's own immune cells. And then we
genetically modify and reprogram those cells outside the
patient's body in the lab, to allow them to express receptors
to proteins that exist only on cancer cells. And by doing so
you allow those immune cells to recognize those cancer cells
more easily and, and eradicate them. So what's unique about
this type of therapy is that, unlike chemotherapy, which
destroys all the rapidly dividing cells in the body,
whether they are cancerous or healthy, CAR T-cell therapy
seems to target the cancer cells. It's also considered
living drug, meaning that the cells are intended to remain in
the patient's body for months or even years, preventing cancer
from coming back.
So once the
patient is evaluated by a transplant physician, and he or
she is deemed eligible for car T-cell therapy, the T cells of
those of the patient will be collected via a procedure called
apheresis or leukapheresis. And in which the patient, which
is a simple procedure done at the clinic as an outpatient, the
patient does not need to be admitted to the hospital. It's
very well tolerated. Once those T-cells are collected, they're
sent to a specialized lab where they are genetically modified or
reprogrammed to target a specific type of cancer. And
then those genetically modified cells are expanded in
the lab by growing them until there are millions of them. And
the process of genetically engineering those cells and then
growing them in the lab will take up too few weeks. And when
there are enough quantities of those cells, they are frozen and
sent back to the center or the hospital when the patient is
being treated. Before the patient receives those CAR T-cells,
he or she will receive few doses of chemotherapy that
are intended to create a space in the immune system for those
cells to expand and proliferate. And then the patient will be
admitted to the hospital for the actual infusion of car T cells.
So the
complete remission rate in non-Hodgkin lymphomas that are
treated with car T-cell therapy varies between 35 to 70% on
clinical trials, and of that number, about a third will
sustain a prolonged and long lasting remission meaning cure,
but some of those patients will not have permanent remissions.
On the other hand in acute lymphoblastic leukemia, the
success rate or the rate of complete remission is even
higher. So 80 to 90% of those patients will achieve complete
remission. However, unfortunately, a significant
portion of those patients will relapse eventually if we do not
consolidate their treatment with allogeneic stem cell transplant.
So again, these complete remission rates and success
rates we're seeing are seen in patients with highly aggressive
types of cancers that oftentimes have stopped
responding to other forms of therapies. And, therefore, and
historically curing those patients and those cases has
been very, very challenging, with very little success using
conventional therapies such as chemotherapy and that's why
people are very excited about the use of car T-cell therapies
in those cases.
So, car-T cell therapy is only approved by the FDA and other regulatory authorities for specific types
of blood and bone marrow cancers. So, there are strict
criteria that the patient must meet before he or she can be
eligible for car T-cell therapy and this criteria varies
depending on the subtype of cancer that the patient has.
Currently, the FDA approves CAR T-cell therapy for
one of four categories of disease. The first one is some
forms of highly aggressive, relapsed refractory non-Hodgkin
lymphoma. The second category of disease that the FDA approved
CAR T-cell for is relapsed refractory follicular
lymphoma which is an indolent lymphoma, and then relapsed
refractory multiple myeloma and relapsed refractory acute
lymphoblastic leukemia. Generally speaking, if you have
one of those diseases, and you have not responded to other
forms of therapies such as chemotherapy or or stem cell
transplant, then you may be eligible for CAR T-cell therapy.
So, most patients do not experience the common side
effects of chemotherapy such as hair loss, nausea, vomiting,
however, they are at risk for severe but short term and
manageable side effects. And that's why we monitor them in
the hospital for a week or two to ensure that there is no such
a reaction to CAR T-cells, the long term effect of CAR T-cell
therapy may not be known for a while because those therapies
are relatively new. However, we do have 10 years experience with
CAR T-cell therapies and we have not seen any unpredicted long term effect of the cells so far.
So, we do admit patients for CAR T-cell therapy to the hospital for a week or two to monitor for any
side effects. But then the patient should expect recovery
period of few weeks following discharge from the hospital will
require the patient to stay within driving distance from the
hospital and they should have care a 24 hour caregiver that
the that looks after them.
Because this therapy is highly specialized and highly personalized. It's given only at
a limited number of centers in the United States with special
expertise in cellular therapy, and the transplant immunotherapy
program at MedStar Georgetown University Hospital is one of those centers
that are certified to give CAR T-cell therapy to patients.
So a patient should be referred to a transplant program as soon as
they stop responding to other forms of therapies such as
chemotherapy. But a couple of studies have shown recently that
some of those patients who relapse within 12 months from
initial therapies could actually benefit from CAR T-cell therapy
as opposed to autologous stem cell transplant which has been,
again, the standard of care for years. Because of these constant
changes and indications for CAR T-cell therapy and because of
the complexity of the logistics of obtaining CAR T-cell therapy,
we highly recommend that those patients are referred to
transplant programs as seen as soon as they relapse following
initial therapy.
So the criteria we go by to determine whether a patient is a good candidate for CAR T-cell therapy is actually
more relaxed than the criteria we use for autologous stem cell
transplant, which again has been the standard of care for years
for lymphoma. For one, we don't have a specific age above which
we don't consider patients to be not eligible for CAR T-cell
therapy. This is in contrast to stem cell transplant in which
most institution will require the patients to be at the age of
70-75 or younger. Secondly, those patients need to have a good
performance status, meaning that they cannot be in wheelchairs or
bedridden. They have to be able to perform some of their or most
of their daily activities without needing significant
help. Finally, the patient needs to be in a good health,
meaning that there is no significant heart disease, lung
disease, liver disease or kidney disease and we do evaluate the
patient's organ functions before we take them to transplant to
ensure that they are going to tolerate the therapy well.
We do also screen them for any active infections that could get
worse after CAR T-cell therapy, or any dormant
infection that could get reactivated after CAR T-cell
therapy.
So, CAR T-cell therapy is a newer type of cancer treatment that may be a little bit more expensive than other
treatments. Not all insurance policies provide coverage for
CAR T-cell therapy. We work with patients and insurers to seek
coverage for CAR T-cell therapy when it's clinically eligible.
And that could include any appeal processes with the
insurance companies.
CAR T-cell therapy has the potential of changing the course of treatment for a variety of cancers not
just blood cancers, but also solid cancers and there are
actually numerous and ongoing clinical trials trying to test
those CAR T-cell therapies in a variety of cancers.
CAR T-Cell therapy is a life saving treatment. And we're proud here
at MedStar Georgetown University Hospital to being able to offer
that treatment to patients whose cancer has stopped
responding to other treatments and we're committed at the
transplant program to bring those cutting edge therapies to
these patients and help them navigate through the
process and make the journey as smooth as possible.