Is CAR T-Cell Therapy Right for My PMBL?

If you have primary mediastinal B-cell lymphoma (PMBL), you’ve likely heard about CAR T gene therapy. There’s good reason for that. Loretta Nastoupil, MD, will tell you, “It’s just the most exciting thing that’s happened in a long time, and potentially is life-saving for many [people].”

She’s quick to add though, “It’s not for everybody.”

Nastoupil is a director at the MD Anderson Cancer Center in Houston, where they’ve been running clinical trials on the therapy. So far, only one type of CAR T, axicabtagene ciloleucel (Yescarta), has FDA approval to treat PMBL.

It’s all very new, exciting, and sometimes confusing. It helps to start with what the therapy’s about and when it might be a good fit for you.

What Is CAR T?

As Nastoupil puts it, “We’re using the body’s own natural defense to eliminate the tumor.” That’s where T cells come in. They’re one of your immune system’s main types of germ killers. The problem is that they don’t always know to go after cancer cells. 

But scientists can now modify their genes so T cells grow a protein called chimeric antigen receptor (CAR). That turns your normal T cells into CAR T cells, which is a game changer. Caron Jacobson, MD, medical director at the Dana-Farber/Brigham and Women’s Cancer Center, says, “The CAR T cells have been trained to recognize and fight the lymphoma the way they would fight an infection.”

The therapy goes like this:

  • You get hooked up to a machine that filters out your T cells and sends the rest of your blood back to your body.
  • Your T cells go to a lab, where scientists change them into CAR T cells. This takes about a week.
  • You get a round of chemotherapy over 3 days -- not to treat the cancer, but to give the CAR T cells the best shot at working.
  • Two days later, you get the CAR T cells, which get to work attacking your PMBL. 

The hard part tends to be waiting for your cells to come back from the lab, Nastoupil says.

That’s because your cancer might get worse during that time, which is a big part of deciding if the treatment’s right for you. Your body needs to be strong enough to get through the wait.

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When CAR T Might Be Right

The FDA has very specific rules about when doctors can use CAR T for PMBL. Unless you’re in a clinical trial, you can only get it after two other treatments have failed, meaning they didn’t work at all, or your cancer came back.

That first treatment is often R-EPOCH, a combination of chemotherapy and immunotherapy. R-CHOP is another regimen that is sometimes given first.

With PMBL, Nastoupil says, “The vast majority of [people] are cured with their first treatment. So there’s a small minority where CAR T will ever even be discussed as an option.”

Your second treatment is usually another type of chemo. But when R-EPOCH doesn’t send your cancer into remission, Jacobson says, “That’s a very worrisome finding." She added that it's also a good clue that more chemotherapy won't work.

So if your first treatment doesn’t stop your PMBL, talk to your doctor about CAR T-cell therapy sooner rather than later. You may still need to try another treatment, but you can lay the groundwork for CAR T, just in case.

Why Not Start With CAR T?

When you’re a good candidate for CAR T, you might wonder why you had to go through chemo first. It’s a fair question.

Nastoupil says, “We have years of experience and know exactly how many [people] we can cure with chemotherapy. And so you hesitate to wipe out all that knowledge and advances that have been made just because you have something new.”

R-EPOCH cures about 9 in 10 people. The problem is that doctors can’t tell ahead of time who it’s not going to work for. 

When to Avoid CAR T

If two different therapies haven’t cured your PMBL, CAR T still might not be right for you.

“So far, what we know is that if you have active autoimmune disease, you’re not a good candidate for this,” Nastoupil says. The same is true if you have an active infection or any problems that affect your brain, like seizures that aren’t well-controlled.

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“We want people’s heart function to be good," Jacobson says. "We want people’s breathing function to be good. We want people’s liver and kidney function to be good enough to go through this therapy. So if they were stressed, even if it’s a limited period of time, it would be less potentially life-threatening."

Also, PMBL can lead to fluid underneath your lungs or around your heart. “That may be a reason not to treat somebody,” says Jacobson. That’s because CAR T can make it worse, which can lead to more serious problems.

Will It Work?

CAR T therapies are very new. And while there were people with PMBL in the studies, there weren’t a lot of them. That makes it hard to say exactly how things will turn out.

What we do know is that the overall results, which include other types of cancer, were very promising. In the Yescarta study that led to FDA approval, more than half the participants had no cancer found after treatment.

You’ll get a PET scan about a month after you get the CAR T cells, which will tell you a lot. “Patients who have a complete response at that point usually do very well,” says Nastoupil. 

Look Ahead, Just in Case

As much attention as CAR T gets, you can't get it everywhere. You might also have to work closely with your insurance company, which can delay treatment.

So Nastoupil suggests that if it looks like you might want to get CAR T therapy, “Start talking to doctors about where you need to go to have access to it.” 

WebMD Feature Reviewed by Laura J. Martin, MD on May 06, 2018

Sources

SOURCES:

Caron Jacobson, MD, medical director, Immune Effector Cell Therapy Program, Dana-Farber/Brigham and Women’s Cancer Center.

Loretta Nastoupil, MD, director, Lymphoma Outcomes Database, University of Texas MD Anderson Cancer Center.

Leukemia and Lymphoma Society: “Chimeric Antigen Receptor (CAR) T-Cell Therapy.”

National Cancer Institute: "CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers."

FDA: "FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma."

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