Understanding CAR T-Cell Therapy
- In a move that could dramatically expand access to a revolutionary new treatment, the FDA has eliminated some of the safety restrictions for CAR T-cell therapies, potentially allowing many more hospitals and doctors to give them.
- Safety restrictions are being lifted because the FDA notes these drugs are more widely understood now and the benefits for patients outweigh the risks.
- CAR T-cell therapy offers the possibility of long-term remission, even cure, for some patients battling blood cancers, including lymphomas, various forms of leukemia, and most recently, multiple myeloma.
- Some CAR T-cell patients may experience potentially life-threatening side effects like neurotoxicity and cytokine release syndrome (CRS). It’s important for patients to carefully weigh the potential risks vs. benefits with their doctors.
The FDA removed regulations, which are called Risk Evaluation and Mitigation Strategies (REMS), paving the way for more access. The regulations were initially added because these CAR T-cell therapies, which rev up a patient’s immune system, can have significant side effects.
Read More“Eliminating the REMS that is no longer needed also expedites the delivery of potentially curative treatments to patients and reduces burden on providers.”
It’s important to understand that CAR T-cell therapy is often described as a “living drug” because it uses your own immune cells, which are reprogrammed to fight a unique aspect of your cancer. Ultimately, these re-engineered cells take over the cancer-fighting work of your immune cells — a truly impressive and completely personalized treatment.
CAR T-Cell Therapy: A Step-By-Step Guide to Having This Breakthrough Treatment
Despite the newly eliminated restrictions, the potential risks linked to these CAR T-cell therapies still exist and products will still come with warning labels about side effects like cytokine release syndrome and neurological issues.
Expert Resources On CAR T-Cell Therapies
- CAR T-Cell Therapy Side Effects Can Be Serious, But Many Are Short-Lived
- CAR T-Cell Therapy: A Step-By-Step Guide to Having This Breakthrough Treatment
- CAR T-Cell Therapy: How it Works, and Who Can Get It
- CAR T-Cell Therapy: Making Your Body a More Efficient Cancer Fighter
- CAR T-Cell Therapy: Why Finding the Right Cancer Center Matters
Potential Side Effects of CAR T-Cell Therapy
Every medical treatment can cause side effects — and CAR T-cell therapy is no exception.
A potentially life-threatening side effect is cytokine release syndrome (CRS). The condition can cause fever, fatigue, and issues with blood pressure, among other symptoms. CRS can be mild for some, requiring little intervention, but it can also be severe.
CRS occurs when the activated T cells recognize the cancer cell antigen they’re designed to attack.
“The T cells actually recruit more T cells to come to the environment. They do this by creating chemicals called cytokines to get into the blood and say the equivalent of ‘Bring the cavalry, bring everybody to this area, let’s go kill this thing now!'” Dr. Thomas Martin, hematologist-oncologist at the University of California San Francisco Medical Center, previously told SurvivorNet.
What is Cytokine Release Syndrome (CRS) and How is It Managed?
The issue is that these chemicals can overwhelm the system. “We see this in the first one to three days after the altered T cells are infused,” Dr. Martin explained.
“The cells go to the area where the [cancer] is, and they grow and expand very quickly. So within 24 to 72 hours most people have symptoms of CRS. Those symptoms include a high fever of 101 to 103 degrees. And they may have low blood pressure or high blood pressure and shortness of breath. Most patients feel fatigued. It feels like you have a bad infection.”
Other possible symptoms of CRS include headache, chills, scratchy throat, nausea, vomiting, diarrhea and muscle or joint pain. In addition, CRS can cause rapid heart rate. All of these symptoms are caused by the new T cells creating a storm inside the body.
“If the symptoms are mild — meaning that the temperature might rise but the blood pressure is fine and there’s no change in the oxygen saturation in the blood — then we can usually just give acetaminophen (Tylenol) to control the fever,” Dr. Martin explained.
“But if the oxygen level gets a little bit low in the blood, some people will need oxygen support by either a nasal cannular or face mask. Or if the blood pressure gets a little low, we give fluids or medication for that.”
In addition to CRS, patients undergoing CAR T-cell therapy might experience side effects like:
- Neurological symptoms (confusion, difficulty speaking or understanding language)
- Drowsiness
- Agitation
- Seizures
- Balance problems
- Altered consciousness
In some cases, CAR T-cell therapy can also lower white or red blood cell counts.
Most side effects are temporary and either resolve on their own or can be treated with medication. However, it’s important for patients to report any symptoms to their doctor or care team right away.
Although CRS can be serious, it is generally manageable. “We see it in 70 to 90% of patients undergoing CAR T-cell therapy, but we anticipate it and know how to treat it,” Dr. Martin said. “And when it passes, the goal is that the patient has experienced a strong anti-cancer response.”
Who Can Get CAR T-Cell Therapy?
The approved CAR-T therapies affected by the FDA’s removal of safety restrictions are: Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel).
For adult patients with multiple myeloma, Abecma (idecabtagene vicleucel) or Carvykti (ciltacabtagene autoleucel) can be used.
For those battling specific types of non-Hodgkin lymphoma — large B cell, chronic lymphocytic, follicular, and mantle cell — Breyanzi (lisocabtagene maraleucel) can be used.
Patients with large B-cell lymphoma might also benefit from Yescarta.
Meanwhile, Kymriah (tisagenlecleucel) can be used to treat patients with B-cell acute lymphoblastic leukemia (ALL) and Tecartus (brexucabtagene autoleucel) can be used for treating mantle cell lymphoma (MCL) and B-cell precursor acute lymphoblastic leukemia (B-ALL).
How CAR T-Cell Therapy Works
The entire process involved in getting CAR T-cell therapy can take a few weeks. It starts by drawing your blood and separating out the T cells.
Then, using a virus that’s been modified to be harmless, the T cells are genetically modified to produce proteins called chimeric antigen receptors (CARs) on their surface. These receptors will enable the cells to recognize and attach to a matching protein, called an antigen, on the tumor cell just as a key fits into a lock. The process primes the T cell to “recognize the cancer and to fight it,” Dr. Julie Vose, the Chief of the Division of Oncology and Hematology at the University of Nebraska Medical Center/Nebraska Medicine, previously told SurvivorNet.
The engineered cells are multiplied into the millions in a laboratory, and then a significant number of them are used to fight the cancer.
The CAR T cells are specific to a patient’s cancer. For example, some types of lymphoma cells have the antigen CD19 on their surface. CAR T-cell therapies for those cancer types only target the CD19 antigen.
A few days before the actual infusion, chemotherapy is used to clear out some of the patient’s immune cells and prime their body to receive the CAR T cells. This will help the CAR T cells work better. Finally, the modified T cells will be infused back into the patient’s body to hunt down the cancer.
Careful Monitoring Is Key
Treatment doesn’t end after the CAR T cell infusion. “They typically have to be monitored very carefully after that for a number of weeks or even months, due to some of the potential side effects,” Dr. Vose explained.
RELATED: A Mom of 4 Diagnosed With Leukemia While Pregnant Finds Hope In CAR T-Cell Therapy. How This Treatment Is Game-Changing for Blood Cancer Patients
As CAR T-cells multiply in the body, they release inflammatory proteins called cytokines. This frequently triggers CRS and may lead to other side effects as well.
WATCH: CAR T-Cell Therapy Side Effects
When side effects do appear, the most common and least severe is fatigue. “That’s very normal, and it usually resolves in the first month,” hematologist Dr. Nina Shah previously told SurvivorNet.
Currently, scientists aren’t sure whether the side effects correlate with how well the treatment is working, so it’s difficult to tell patients whether their side effects or lack of them are a good or bad thing. “All I can say is that every patient is different, and every patient has a different course,” Dr. Shah said.
Data shows that the quality of life for people who have undergone CAR T-cell therapy “actually improves when we talk about pain, fatigue, and emotional and social functioning. And so, whether or not you experience side effects, we hope that this therapy will improve your quality of life,” she added.
If you’re considering CAR T-cell therapy, talk with your doctor about all potential side effects — the mild, the serious, and how they will be monitored and managed.
Contributing: SurvivorNet Staff
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