Alaa Ali, MD, MSC, is a clinician, instructor, and investigator in clinical and translational research at MedStar Georgetown’s Stem Cell Transplant and Cellular Immunotherapy program.
In the following video, Dr. Alaa Ali explains what CAR T-cell therapy is and how it works, what the process is for creating CAR T-cells to fight cancer, the success rate of CAR T-cell therapy and much more.
Video Transcript:
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..