Breaking Down What CAR T-Cell Therapy Means for Blood Cancers

Chimeric antigen receptor T-cell (CAR T) therapy is a type of immunotherapy that some patients with blood cancers may be eligible for to treat their cancer. The therapy re-engineers existing immune cells to attack cancer cells, offering an innovative and targeted form of therapy, according to Dr. Olalekan O. Oluwole, malignant hematologic disorders treatment specialist.

Oluwole works at the Vanderbilt Hematology Clinic, which is part of the Vanderbilt-Ingram Cancer Center, a cancer center located in Nashville, Tennessee, which offers CAR T-cell therapy. To delve deeper into the topic of CAR T-cell therapy, and the possibility of treating patients with CAR T-cell therapy in an outpatient setting, he sat down for an interview with CURE, where he explained how CAR T is used to treat high-risk blood cancers.

Oluwole is also an associate professor of medicine in the Division of Hematology Oncology, Department of Medicine, at Vanderbilt University Medical Center.

CURE: Can you explain how CAR T-cell therapy is used to treat high-risk blood cancers like leukemia and lymphoma?

Oluwole: I treat patients with leukemia and lymphomas, particularly those with high-risk lymphoid malignancies, using cell therapy, also known as CAR T-cell therapy, for the most part.

What are CAR T-cells? It's a new way of treating cancer where we harness certain qualities of the immune system so we can effectively use them to eradicate leukemia, lymphoma, or any other tumor. This is important because, while we have traditional chemotherapy, sometimes it doesn't work. The lymphoma or cancer figures out a way to either hide from the immune system or to fool the immune system into tolerating it. That's what we aim to overcome with CAR T-cell therapy.

How do we do this? We harvest immune cells from a patient, or we can also use healthy donor immune cells. These are mature immune cells that we harvest, and they are genetically modified a little bit so they can be targeted to identify something present on the lymphoma or leukemia cells. Once that manufacturing process is complete, those same immune cells are then infused into the patient. They go directly for the leukemia or lymphoma cells and continue to attack them until they have eradicated the last one.

Whereas patients who receive chemotherapy and it doesn't work might die from their leukemia or lymphoma, there is actually a potential for cure with CAR T-cell therapy because these immune cells sometimes go after the tumor and get rid of the very last cancer cell. In lymphoma, we've found this happens more than half the time, which is really reassuring for patients who otherwise would have had no other real treatment options.

How does receiving CAR T-cell therapy in an outpatient setting compare to traditional inpatient administration experiences?

These immune cells, because they are engineered, are really focused on taking out their target, and the way they know to engage anything, for that matter, is by triggering an immune response. For example, the immune system is naturally aimed at eradicating bacteria and viruses and organisms like that. They cause a fever; they cause inflammation. So that is how they know to fight. What happens is that they engage the leukemia and lymphoma exactly the same way that they would have engaged a microorganism. They can get really revved up against the lymphoma.

They cause very high-grade fevers, they can cause low blood pressure, sometimes altered mental status, and sometimes neurological problems. For those first two weeks after the CAR T is administered to the patient, we need to monitor them very closely so that when they are revved up too high, we can tamp down the immune system by giving Tocilizumab or a few doses of corticosteroids. This ensures they don't get super revved up to the extent that it can hurt the patient. We have methods with which we can tamp down those responses.

If we go back to around the time that we started to give CAR Ts, we were learning as we went. All those patients were treated in the inpatient setting, often staying in the hospital for two weeks or longer, sometimes with trips to the intensive care unit. But you see, we are investigators; we learn quickly, we learn fast, and we develop protocols to actually manage these patients. We have figured out ways to make the treatment a lot safer now than it was early on. We've even figured out preemptive treatments that we can give that can also make the whole treatment more tolerable.

What impact has the shift from inpatient to outpatient care had on patient safety and quality of life?

That was actually what brought up the question: “Okay, fine. When we started all of this, we had to put them in the hospital for two weeks or longer. We now have almost 10 years’ worth of data in certain instances. Do we really need this? Is there a way that this can be made more tolerable to the patients?” And if we also remember that it's not that the hospital is not a good place to be; a patient that is in the hospital, you know where they are at every point in time, and you can easily get interventions done very quickly. That's why the hospital is such a desirable place. But unfortunately, being in the hospital comes with other things.

We are really good at many things, but the quality of life for patients outside of the hospital is unquestionably better. So that's why my colleagues and I devised this method: we would just start all of these outpatient. We will infuse the CAR T in the outpatient setting, and we will start to monitor these patients in the outpatient setting. All the safety methods that we had designed over the years, we would deploy them to manage the patients. Many will stay out as long as they could, and if they needed to come in, we have a method that can rapidly get them in, so that whatever interventions we need to give to them will be known in under one hour. With this assurance, we were able to roll out all our programs to the outpatient setting, only admitting those who needed to come in.

We were pleased to see the results that we now use about one-third as many hospital days as it was in the beginning when we were putting everybody in the hospital for the whole time.

Transcript has been edited for clarity and conciseness.

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