If you or a loved one has diffuse large B-cell lymphoma (DLBCL) that is no longer responding to treatment or came back after treatment, chimeric antigen receptor (CAR) T-cell therapy may be an option. Here's what you need to know.
What Is CAR T-Cell Therapy?
It's a type of immunotherapy that uses your body's own white blood cells to fight your lymphoma. It uses a particular kind of white blood cell known as T lymphocytes, or T cells. Doctors remove them from your body, change them in a lab so that they target lymphoma cells, and then put them back into your body, where they go to work killing cancer cells.
To help make sure your body doesn't reject the CAR T cells, you'll typically be given 3-4 days of chemotherapy a few days before you receive them. This is to tamp down your immune system by reducing the number of immune cells in your body. Then the CAR T cells can go to work.
After the treatment, your doctor will watch you carefully for about a month for side effects, because some of them can be serious. An inflammatory condition known as cytokine release syndrome can happen once your immune system goes to work killing the cancer cells. It usually requires treatment in a hospital for symptoms that include fever, chills, nausea and vomiting, breathing problems, and pain. Brain problems such as headaches and confusion are also common.
Research has shown that about 1 in 5 people who get CAR T-cell therapy will need follow-up care in the ICU, usually within the first 4-5 days.
What Are the Approved Therapies?
The FDA has approved three CAR T-cell therapies for use in adults with DLBCL:
- Axicabtagene ciloleucel (Yescarta)
- Lisocabtagene maraleucel (Breyanzi)
- Tisagenlecleucel (Kymriah)
A handful of other CAR T-cell therapies for DLBCL are under development. Some therapies, like ALLO-501A, have reached phases I and II of clinical trials.
When Is CAR T-Cell Therapy Usually Given?
Currently, the CAR T-cell therapy tisagenlecleucel (Kymriah) is only approved by the FDA as a third-line treatment for DLBCL. This means that, to be eligible, you need to have already tried at least two other kinds of treatments. DLBCL is almost always treated first with chemotherapy and drugs called monoclonal antibodies that attack cancer cells; 60% to 70 % of patients go into remission after this.
For those who don’t, the second-line treatment is usually more chemotherapy followed by a combination of high-dose chemotherapy and a stem cell transplant. This is sometimes called “salvage” treatment. People who don’t respond to these treatments or whose cancer comes back usually don’t have a good prognosis. This has been when doctors turn to CAR T-cell therapy.
CAR T-Cell Therapy Given Earlier in Treatment
The CAR T therapies axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi) are sometimes used as a second-line treatment after a single round of chemotherapy or as third-line treatment. Some recent studies showed that after just one round of chemotherapy, people with aggressive B-cell lymphoma who had CAR T-cell therapy lived longer without their lymphoma getting worse, as compared to those who received the standard treatment.
There are other benefits to the use of CAR T-cell therapy as a second-line treatment. The treatment time is shorter, and with fewer aggressive chemotherapy treatments, recovery is also shorter and may be somewhat easier for some people.
What Is the Success Rate of CAR T-Cell Therapy?
More research is needed, but some studies have shown that up to 70% of B-cell lymphoma patients are still alive a year after treatment, and that the results of CAR T-cell therapy can last 5 years.
Other research has found that relapse is common: One study of 116 people with aggressive B-cell lymphomas found that nearly half of them relapsed within 8 months of getting CAR T-cell therapy. Overall, experts estimate that the success rate – meaning that you're in remission, with no further treatments needed – of CAR T-cell therapy for aggressive B-cell lymphomas is about 30% to 40%.
What's on the Horizon?
Scientists are also exploring how they can fine-tune CAR T-cell therapy. They are experimenting in the lab to create CAR T cells that are more precise and last longer. They are looking at whether CAR T-cell therapy works better when combined with other therapies. And they are also looking into new ways to prevent and manage side effects.
About 100 medical facilities across the country now offer CAR T-cell therapy, and the cost of the procedure can easily add up to $500,000 or more. So researchers are also looking into ways to make the treatment more affordable and widely available.
Show Sources
Photo Credit: Meletios Verras / Getty Images
SOURCES:
Lymphoma Research Foundation: "Understanding Diffuse Large B-Cell Lymphoma," "CAR T Cell Therapy for Lymphoma," “Diffuse Large B-Cell Lymphoma: FDA Updates.”
The Lancet Haematology: "Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study."
Journal of Cancer Metastasis and Treatment: "CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions."
Blood Advances: "Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies," "Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma."
Cochrane: "CAR T-cell therapy for people with diffuse large B-cell lymphoma which returns after treatment or no longer responds to treatment."
HemaSphere: "CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope."
The New England Journal of Medicine: "Five-Year Outcomes for Refractory B-Cell Lymphomas with CAR T-Cell Therapy," “Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma.”
Antibodies: "Tinkering under the Hood: Metabolic Optimisation of CAR-T Cell Therapy."
Blood: "CAR T-cells as a second-line therapy of large B-cell lymphoma: A paradigm shift?"
National Cancer Institute: "Should CAR T Cells Be Used Earlier in People with Non-Hodgkin Lymphoma?"
Nature Biomedical Engineering: "Control of the activity of CAR-T cells within tumours via focused ultrasound."
Science: "Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling."
European Journal of Inflammation: "Recent advances in the prevention and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy."
American Journal of Managed Care: "Improving Outcomes and Mitigating Costs Associated With CAR T-Cell Therapy."
American Cancer Society: “CAR T-cell Therapy and Its Side Effects.”
MD Anderson Cancer Center: “9 things to know about CAR T-cell therapy.”
RWJ Barnabas Health: “Advantages of CAR-T Cell Therapy.”
Allogene Therapeutics: “Allogene Therapeutics Announces Removal of FDA Clinical Hold Across All AlloCAR T Clinical Trials.”
Blood: "Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study."
News release, FDA.
UpToDate: "Diffuse large B cell lymphoma (DLBCL): Suspected first relapse or refractory disease in medically-fit patients."
