FDA Investigating CAR T-Cell Therapy Risk For Risk of Causing Secondary Cancers
- The Food and Drug Administration (FDA) is investigating the safety of CAR T-cell therapy, which is often used to treat certain blood cancers, because of the risk of developing T-cell malignancies in patients.
- CAR T-cell therapy uses your own modified immune cells to fight cancer, but it can have side effects, including cytokine release syndrome (CRS), which gives patients flu-like symptoms.
- This treatment can also affect the brain, causing confusion and difficulty speaking. Doctors closely monitor for these and other side effects after treatment and have therapies to manage them.
- Several FDA-approved CAR T drugs are on the market to treat blood cancers, including lymphomas, some forms of leukemia, and, most recently, multiple myeloma.
The FDA says it received reports of “T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with B-cell maturation antigen (BCMA) or B-lymphocyte antigen (CD19) directed autologous CAR T-cell immunotherapies.”Read More
Once the re-engineered cells are re-inserted into the body, the T-cells find and attach to a matching protein called an antigen on the surface of the cancer cells.
Dr. Siddhartha Ganguly is a Carol Cockrell Curran Distinguished Centennial Chief in Hematologic Oncology at Houston Methodist Hospital and Neal Cancer Center. He describes the process of making CAR T-cell therapy a reality, similar to the popular video game Pacman.
“CAR-T therapy aims to give “eyes” to the T-cells. We remove the T-cells from the body by a blood draw, send them to the lab, and insert an anti-cancer gene before infusing them back into the patient. This gene allows the T-cell to “see” the cancer cells…They will seek out the cancer and kill it, much like the video game Pacman,” Dr. Ganguly told SurvivorNet.
Dr. Ganguly says he’s been using this form of treatment on patients for years and emphasizes the hope it offers to patients battling diseases like advanced lymphoma or myeloma. He adds that although CAR T-cell therapy, like most treatments, has its side effects.
The FDA has approved the following drugs so far:
- Abecma (idecabtagene vicleucel)
- Breyanzi (lisocabtagene maraleucel)
- Carvykti (ciltacabtagene autoleucel)
- Kymriah (tisagenlecleucel)
- Tecartus (brexucabtagene autoleucel)
- Yescarta (axicabtagene ciloleucel)
These drugs help treat blood cancers like lymphomas, some forms of leukemia, and, most recently, multiple myeloma. While these therapies offer potential benefits for patients impacted by various cancer types, the FDA is investigating the risk of T-cell malignancy in CAR T-cell therapy.
Dr. Ganguly says the FDA investigation should not cause panic but stresses physicians and patients should remain vigilant.
“This most recent warning by the FDA concerns the anti-cancer gene introduction into the t-cells, which is done in the lab. In some situations, if the genes integrate – in most cases, we have minimal control – into the wrong spot on the T-cell, the T-cell itself can become cancerous. We are aware that this can happen, which is why we follow patients who receive CAR-T therapy for many years so we can monitor them closely for this type of complication,” Dr. Ganguly said.
He adds although safety risks exist, “this particular complication is exceedingly minimal.”
Dr. Frederick Locke, the chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department and co-leader of the Immuno-Oncology Program at Moffitt Cancer Center, tells SurvivorNet he still sees the value in CAR T-Cell therapy but is awaiting more data.
“Thousands of patients have received treatment for cancer with FDA-approved CAR-T cell therapies. To date, I am unaware of any peer-reviewed reports of T cell lymphomas positive for the Chimeric Antigen Receptor with these approved therapies. That said, it is not out of the realm of possibility that one or two out of ten thousand patients could develop T cell lymphoma,” Dr. Locke said.
WATCH: Is CAR T-Cell Therapy right for you?
Dr. Locke noted rare cases of CAR T-cell therapy contributing to the progression of some blood cancers. However, he also added that immunotherapy has also rarely contributed to lymphoma, a type of blood cancer.
“We know that cancer immunotherapy such as checkpoint blockade for solid tumors, which does not rely on gene therapy, can very rarely result in T-cell lymphomas,” Dr. Locke added.
Helping Patients Better Understand CAR T-cell Therapy
What’s the Effectiveness of CAR T-cell Therapy?
CAR T-cell therapy has shown a response rate as high as roughly 80 percent in some blood cancers after other treatments have failed. In lymphoma, more than 54% of people who took the FDA-approved CAR T-cell therapy axicabtagene ciloleucel (Yescarta) and 40% of those who took tisagenlecleucel (Kymriah) achieved a complete response, meaning they no longer had any sign of cancer in their body. With Yescarta, 40% of people were still in remission an average of 15 months after their treatment.
Those who get CAR T-cell therapy have already been through at least two other treatments — usually rituximab (Rituxan) plus chemotherapy, as well as high-dose chemotherapy. “Some of these patients had three, four, or five prior lines of therapy, and we were able to save their lives,” Dr. Stephen Schuster, director of the Abramson Cancer Center’s lymphoma program, tells SurvivorNet.
CAR T-Cell Therapy Side Effects
CAR T-cell therapy differs from chemotherapy cancer treatment because it doesn’t cause hair loss and nausea. However, it still has side effects. When CAR T-cells multiply in the body, they trigger the release of inflammatory chemicals called cytokines. This can lead to a condition known as cytokine release syndrome (CRS), with symptoms such as high fevers, weakness, chills, and low blood pressure. Another possible side effect of CAR T-cell therapy is brain changes that can lead to confusion and a lack of awareness.
WATCH: CAR T-Cell Therapy Side Effects
When side effects do occur, the mildest one is fatigue.
“That’s very normal, and it usually resolves in the first month,” says hematologist Dr. Nina Shah.
A more serious side effect of CAR T-cell therapy is called cytokine release syndrome (CRS). CRS occurs when the CAR-T cell therapy causes a significant, rapid release of cytokinessmall proteins that are part of the immune system into the circulation. That release can cause a variety of reactions. The flu-like symptoms of CRS can include headache, fever, chills, scratchy throat, nausea, vomiting, diarrhea, muscle or joint pain, and lack of energy. In addition, CRS can cause shortness of breath, low blood pressure, and fast heart rate. Most people who develop CRS will have mild to moderate symptoms, but sometimes, CRS can be severe and even life-threatening.
If CAR T-Cell therapy is a treatment option, you should discuss all possible side effects with your doctor.
SurvivorNet will continue to follow this story and the FDA investigation as it develops.