Step-by-Step Guide to CAR T-Cell Therapy

The Making of CAR T Cells 

Next, the hospital ships your T cells to a lab at the company that makes the CAR T product you're getting. CAR T therapies that are FDA-approved for DLBCL are:

• Axicabtagene ciloleucel (Yescarta)
• Lisocabtagene maraleucel (Breyanzi)
• Tisagenlecleucel (Kymriah)

Each company's process to make CAR T cells is a little different. In general, the first step is to separate the T cells from your other white blood cells. Then the lab uses a virus to deliver the genetic material (DNA) to turn your T cells into cancer-fighting cells. "Viruses are a really good way of putting things into cells because they infect the cells," Jain says. 

The new genes instruct the T cell to make proteins called chimeric antigen receptors (CARs) on their surface. Then the lab multiplies the CAR T cells until there are millions of them. 

Finally, the lab tests the CAR T cells to make sure there are no germs in them and they meet FDA requirements. "For example, a certain percentage of the cells have to still be alive after manufacturing and a certain percentage of them have to express the CAR T cell," Jain says.

The lab freezes the CAR T cells and sends them back to your hospital, ready to be infused into you. How long this whole process takes varies from one center to another. It should take the lab 2 to 4 weeks to process your CAR T cells and return them to your cancer hospital or treatment center. 

While You Wait

What you do during those 2 to 4 weeks depends on your cancer. If it grows slowly, you may not need any treatment. Your doctor will just monitor you. "But other patients, their lymphoma is growing quite rapidly and they need some sort of treatment. We call that type of treatment bridging therapy," Jain says.

Bridging therapy can involve different treatments. If the cancer is only in one area of your body, you might get radiation therapy. But if the cancer has spread, you may get chemotherapy combined with immunotherapy, says Madiha Iqbal, MD, a hematologist-oncologist, assistant professor, and consultant at Mayo Clinic in Jacksonville, FL. "It allows us to control the disease until the CAR T cells come back." 

CAR T Infusion

Once your cells come back as CAR T cells, it's time to put them into your body. But first, you'll get low-dose chemotherapy to kill your own T cells. Your doctor calls this treatment lymphodepletion chemotherapy. "Giving lymphodepletion chemotherapy allows the CAR T cells to expand and work better," Iqbal says. Basically, the chemo makes room for your new CAR T cells to grow.

Then the countdown starts. You'll get chemo on days -5, -4, and -3. Day -2 is a rest day when you don't get any treatment. Day -1 you'll go into the hospital if you're staying there overnight. On day zero, you get the CAR T cell infusion through an IV or central line placed into a vein. The infusion takes about 30 minutes.

How CAR T Cells Work in Your Body

Over the next 1-3 weeks, the T cells will multiply in your body. How many times they multiply is unique to you and depends on the size of your cancer. "Patients who have very large lymphomas going into CAR T-cell therapy, their CAR T cells tend to expand more. They need more expansion to be able to overcome the amount of tumor that's there," Jain says.

CAR T cells act like guided missiles. They seek out CD19, an antigen on the surface of lymphoma cells. Antigens are proteins that trigger an immune response in your body. When the CAR T cells attach to CD19, they release chemicals that kill the lymphoma cells.

The CAR T cells can keep working in your body for months or years. How long they stay in your body doesn't affect your outcome. Some people stay in remission long after their CAR T cells are gone. Other people relapse while they still have working T cells, Iqbal says. How your cancer responds to the CAR T cells is unique to you.

After CAR T

This treatment can stop DLBCL from coming back and maintain a long-term remission. CAR T even cures some people.

Yet this treatment can have side effects. CAR T cells release chemicals called cytokines that make your immune system react. Doctors call this cytokine release syndrome (CRS), and it can cause a high fever, low blood pressure, and trouble breathing. CAR T can also affect your nervous system and cause problems like confusion and trouble speaking or understanding. These side effects should improve in a couple of weeks.

You'll need to stay close to your treatment hospital for up to 30 days so your medical team can monitor you for side effects. You may have to stay in the hospital overnight or longer if you have severe symptoms like a very high fever.

"Another really key thing is that patients need a caregiver," Jain says. Someone has to be with you 24 hours a day for the first month after treatment to drive you to the hospital and watch you for side effects.

Long-Term Follow-Up

Your doctor will do imaging tests like a PET or CAT scan about once every 3 months to see how your cancer responded. "Most of the studies have shown that the relapses after CAR T tend to happen in the first 6 months. That's the reason to keep a closer eye [on patients] during this time period to detect relapses," Iqbal says. If your disease stays under control, you may be able to space out your visits to once every 6 months and then once a year.

Expect to see your cancer doctor for up to 5 years after CAR T-cell therapy. These visits are to check for relapses and long-term side effects like infections. After 5 years without a relapse, you may be in the clear. "These are patients who are potentially cured and most likely the disease will never come back," Iqbal says.