CAR T-cell therapy side effects in lymphoma patients
When chemotherapy and radiation fail, some adult patients with B-cell non-Hodgkin lymphoma or children with acute lymphoblastic leukemia have a new treatment option called CAR T-cell therapy. Yescarta is the CAR T-cell therapy that’s FDA-approved to treat patients with B-cell non-Hodgkin lymphoma; it shrinks the tumors in 70-80% of patients.
But with this new therapy come side effects that are different from those of other cancer treatments. To better understand these side effects in adult lymphoma patients, we talked with Felipe Samaniego, M.D.
How does CAR T-cell therapy work?
Like other types of immunotherapy, CAR T-cell therapy uses the patient’s own immune system to treat cancer.
T cells – one type of the immune system’s fighter cells – are extracted from the patient, modified in a lab and then transfused back into the patient.
During the next four weeks, the modified CAR T cells rapidly multiply in the body, building a robust army that finds and attacks the cancer cells.
For about 30 days, patients are also at risk for side effects, some of which can be life-threatening.
What are the side effects of CAR T-cell therapy in lymphoma patients?
To prepare the body for CAR T-cell therapy, patients receive a small dose of chemotherapy, which may cause other side effects, such as fatigue and low blood count.
As the CAR T cells work to fight cancer, they cause the release of large amounts of other T cells into the blood, along with cytokines, which are proteins released by cells that communicate to other cells that there’s a job to be done. This effect triggers the production of even more T cells, all of which can lead to side effects. We categorize these side effects into two categories: cytokine release syndrome and CAR T-cell-related encephalopathy syndrome.
Cytokine release syndrome side effects mimic what it’s like when T cells attack a virus. So, patients feel like they’re fighting a severe case of the flu, but really they’re fighting cancer. Patients may experience fever, weakness, chills and loss of appetite. These side effects typically start a few days after the CAR T-cell transfusion and last about a week.
CAR T-cell-related encephalopathy syndrome side effects are less common but more severe because they involve the brain. Patients may experience confusion, irritability, lack of awareness or may have difficulty recognizing family and friends. Signs of CAR T-cell-related encephalopathy syndrome show up around one to four weeks after the transfusion and last two to four days. While these side effects can be upsetting, they’re reversible most of the time.
How are CAR T-cell therapy side effects treated in lymphoma patients?
Our approach is to let the flu-like cytokine release syndrome side effects occur because they’re coming from the cells attacking the lymphoma. But if they’re putting the patient’s health at risk, they can be stopped with an immunosuppressive drug called tocilizumab.
Signs of CAR T-cell-related encephalopathy syndrome, such as being confused and irritable, can quickly escalate, causing other vital systems not to work, too. Some patients lose their ability to speak or have trouble breathing. When the patient’s safety is at risk, we can stop the brain-related side effects by giving a steroid for a few weeks.
But by stopping these side effects, we’re also stopping the CAR T cells from fighting cancer.
How do you ensure a patient’s safety during the side effects?
We have to strike a delicate balance between allowing patients to experience the cancer-killing side effects and stopping the therapy too early. Patients typically stay in the hospital for three to four weeks after the CAR T cells are infused so our trained team can care for them. Even if patients don’t experience many side effects in the hospital, they could have them at home, so our patients come back weekly for check-ups.
Also, we know that patients ages 65 and older are at a higher risk of experiencing the brain-related side effects of CAR T-cell-related encephalopathy syndrome. Older patients have more extensive health histories that may include conditions like diabetes, heart problems or kidney failure that require additional attention. And because the unfamiliar setting of a hospital can be confusing for some older patients, we want to ensure their confusion isn’t related to the treatment.
To better monitor patients for severe side effects, we conduct a physical exam before the CAR T cell transfusion to assess patients’ current health. If you have a history of stroke, seizures, memory loss, lung problems or heart problems, be sure to tell your doctor. And since infection is a risk, also be sure to share if you’ve had a recent infection or if you’re currently fighting one.
As part of that exam before the transfusion, we also test cognitive ability by asking each patient to write a few sentences. Following the treatment, if the patient’s writing skills worsen, we know it’s a sign of distress in the brain.
What CAR T-cell therapy research is underway?
We still have a lot to learn about CAR T-celltreatment and its side effects. We’re working to identify antibodies that may reduce the massive cytokine release and possibly prevent the related side effects.
We’re also exploring combining CAR T-cell therapies with other treatments like immune checkpoint inhibitors to make them work even better. Our goal is to better understand the side effects of CAR T-cell therapy and to expand this treatment’s success to more patients and more cancer types.