Last year, the Food and Drug Administration approved two new immunotherapies to treat certain leukemias and lymphomas. Now, in a study published in the New England Journal of Medicine, researchers detail who is most likely to benefit from the treatments, called CAR T cell therapy.
CAR T cell therapy trains the body’s immune system to target and destroy cancer cells in the blood; scientists take people’s own immune cells (T cells) and genetically engineer them to seek out and destroy cancer cells. The immune system can then attack cancer cells in the same way it does bacteria and viruses, and the therapy can lead to remissions from blood cancers of up to 80%.
But Dr. Jae Park, lead author of the research, says that many of those studies only follow people for a year or so, since CAR T cell therapy is still so new. Park, an assistant attending physician at Memorial Sloan Kettering Cancer Center, studied 53 people with acute lymphoblastic leukemia for up to five and a half years after they received CAR T therapy.
Before getting the one-time infusion of genetically engineered T cells, doctors generally use chemotherapy to eliminate as much cancer as possible. All of the people in the study had received several rounds of chemotherapy but their cancer returned. Park and his colleagues found that people who had the least amount of disease before receiving the CAR T therapy had the longest median survival overall and also experienced the fewest side effects from the treatment, such as potentially fatal brain swelling.
That’s not entirely surprising, but the results have important implications for how doctors will use CAR T cell therapy in the future. First, Park says, the findings suggest that determining how much cancer a person has before getting the treatment could be a good indicator of who will respond best to the therapy and who might not have as robust an outcome.
Second, the findings also confirm what many cancer experts have suspected about how best to deploy CAR T cell therapy: that using the treatment earlier in people’s disease, when their bodies and immune systems are theoretically stronger, might lead to more sustained remissions. Currently, the two FDA-approved CAR T cell therapies are approved for people who have failed existing treatments, including chemotherapy and bone marrow transplants.
“We show that there are durable responses for some beyond five years,” says Park. “But what if we con control the disease burden before it gets too high? After people fail only one or two rounds of chemotherapy, maybe that’s the best time to use CAR T cell therapy. Our data suggest that’s the best setting for long-term benefit. These results provide the groundwork to support that approach.”
Already, Park and his colleagues plan to study people who receive CAR T after just one or two chemotherapy regimens. “Rather than wait until people fail on other treatments, and use CAR T cell therapy to rescue them, we want to be there before they fail so they don’t have to be rescued,” he says. “That way, they will have a better response, and we may come closer to a cure for their disease.”