CAR T-cell therapy has revolutionized treatment for many blood cancers. However, the benefits of its use in the early stages of care remain uncertain.
Chimeric antigen receptor (CAR) T-cell therapy holds promise for people with large B-cell lymphoma (LBCL) and other blood cancers. This innovative treatment creates genetic changes in certain immune cells to better attack cancer cells in the body.
Although it can be highly effective, CAR T-cell therapy may not be effective for everyone. It can also lead to serious side effects, so those with LBCL rarely undergo this technique as a first-line treatment.
A person would typically only receive CAR T-cell therapies after other treatments have been attempted. These approaches generally have approval to treat relapsed or refractory LBCL. The CAR T medications for LBCL are:
Currently, doctors generally recommend CAR T-cell therapy as a third-line or later treatment for LBCL. There is some evidence to support earlier treatment with this method, but it is not conclusive.
A 2024 study found that people with relapsed or refractory LBCL who received CAR T as a second-line therapy had better outcomes than those who received it as a third-line treatment. However, the study did not contain formal statistical comparisons.
A 2022 clinical trial found that CAR T therapy as a second-line treatment in LBCL led to a longer period of event-free survival compared to standard second-line treatment.
In some high risk individuals with LBCL, doctors have explored CAR T-cell therapy as a first-line treatment. However, there is currently no evidence that this technique works better in the first-line setting compared with standard treatments like chemotherapy and stem cell transplants.
CAR T-cell therapy uses a person’s immune cells to target cancer in the body. These cells undergo genetic modification to enhance their effectiveness at fighting LBCL.
The immune system contains T cells, which latch onto and destroy disease cells. The therapy involves adding CAR proteins to T cells that match LBCL cancer cells. CARs make it easier for T cells to attach to and kill the cancer by matching the proteins, called antigens, on the cancer cells.
CAR T-cell treatment for LBCL takes about 3 to 5 weeks. A person receives only one infusion of the medication, but it takes many days for the genetically altered T cells to grow.
In the first stage of therapy, healthcare professionals remove T cells from the person’s body through a process called apheresis. Those cells go to a lab where they undergo genetic modification to target LBCL cells. The lab grows hundreds of millions of those changed cells. Healthcare professionals then administer them back to the person in a single infusion.
After the infusion, the modified T cells should begin to kill cancer cells. The T cells should also continue to multiply in the body in the days and weeks following the infusion.
A person can speak with their cancer care doctor to discuss the possibility of CAR T treatment.
However, not everyone with LBCL is eligible for CAR T-cell therapy. A medical care team should assess a person’s prior treatment experience. Since this technique can have significant side effects, individuals must have adequate organ function to support the treatment.
Some of the side effects include cytokine release syndrome (CRS), where the immune system overreacts to the treatment. Another serious side effect is immune effector cell-associated neurotoxicity syndrome (ICANS), which can cause a range of neurological symptoms.
If a person does not have the financial resources to pay for CAR T therapy, a hospital or clinic may wait for insurance coverage approval before proceeding.
About 60% of people with refractory or relapsed LBCL relapse again or experience disease progression after CAR T-cell therapy. Therefore, only about 40% of individuals do not experience the recurrence or worsening of the cancer after the treatment.
Cancer cells can also become resistant to CAR T-cell therapy. There is a phenomenon of “antigen escape,” where the target protein on the cancer cells becomes undetectable. The cancer cells are still in the body, but the protein that the modified T cells are there to target is no longer expressed.
A person’s modified T cells can also stop working over time, known as T-cell exhaustion. The cells shut down after too much time signalling.
Sometimes the modified T cells do not multiply in the body in the most effective way to fight the cancer. Researchers are just learning how the genetically changed T cells populate in the body. A 2025 study found that there are two distinct periods when the modified T cells clone within the body.
There is some evidence that chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) might lead to better outcomes in the earlier stages of treatment. However, this evidence is inconclusive. CAR T therapy comes with significant side effects, and not everyone is eligible for this treatment. Researchers are continuing to assess the best treatment options for individuals living with this form of blood cancer.
 
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