Why CAR T-Cell Therapy Is So Exciting

By 2010, Bill Ludwig had been living with leukemia for 10 years, and he was out of treatment options. Desperate for something that might work, Ludwig let his oncologist at Penn Medicine’s Abramson Cancer Center enroll him in a clinical trial of a new treatment called chimeric antigen receptor (CAR) T-cell therapy. At the end of his treatment, Ludwig was cancer-free. A decade later, CAR T-cell therapy is an approved treatment for several cancers, including non-Hodgkin lymphoma. And its results continue to excite and amaze oncologists.

“I’ve hit on a couple things in my career that were exciting and hard to believe, and this was one of them,” Dr. Stephen Schuster, director of the Abramson Cancer Center’s lymphoma program, tells SurvivorNet. “Not only did it work, but with a single treatment these patients were not relapsing.”

CAR T-Cell Therapy, Explained

What researchers at Penn figured out how to do with CAR T-cell therapy was to re-engineer patients’ immune cells into more efficient cancer fighters. The process starts with T cells, white blood cells that help the immune system respond to threats in the body such as germs and cancer cells.

In CAR T-cell therapy, doctors first remove T cells from a patient’s blood. Then, they use an inactivated virus to insert new genes into the T cells. Those new genes carry the instructions to create special proteins called receptors on the T cells’ surface. The modified T cells are multiplied into the millions before being given back to the patient.

Once inside the person’s body, the T cells find and attach to a matching protein called an antigen on the surface of the cancer cells. In non-Hodgkin lymphoma, the target is CD19. “They go to the tumor, expand, and amazingly, wipe the tumor out,” Dr. Schuster says. “It’s called cellular therapy.”

Two CAR T-cell therapies are approved for people with diffuse large B-cell lymphoma: axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah).

How Well Does This Therapy Work?

When Dr. Schuster and his colleagues at Penn Medicine were studying CAR T-cell therapy and they first introduced the genetically modified T cells into patients, the results surprised them. “Amazingly, it worked. And it worked in a durable fashion,” he says.

In studies, more than 54% of people who took Yescarta and 40% of those who took 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. Schuster tells SurvivorNet.

When You’re Considering CAR T-Cell Therapy

Though this treatment is exciting, it’s not right for everyone with non-Hodgkin lymphoma. The FDA has approved CAR T-cell therapy for aggressive diffuse large B-cell lymphoma that has come back after treatment or that didn’t respond to treatment. It’s also approved for high-grade B-cell lymphoma and transformed follicular lymphoma.

CAR T-cell therapy doesn’t cause hair loss and nausea like chemotherapy, but it does have its own list of side effects, and some of them can be serious. 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.

Discuss all of the possible side effects of this treatment with your doctor before you start, so you’ll know what to expect, and what to do if you have them.

Learn more about SurvivorNet's rigorous medical review process.