Dr Brian Koffman Highlights the Benefits and Risks of CAR T Therapy

Since chimeric antigen receptor (CAR) T-cell therapy is still in early development there are benefits and risks that eligible patients will have to weigh, including the durable response against the limited amount of data and toxic side effects, said Brian Koffman, MDCM, DCFP, DABFM, MS Ed, medical director, CLL Society.

Transcript

As a patient who was treated with CAR T-cell therapy, what have been the benefits and the challenges?

CAR T therapy is very early in its development. So, making a decision to jump into CAR T therapy has inherent risks associated with it. But I decided the risks were worth the potential benefits, which would be an extremely durable response. There are a number of concerns about that. The first is that we don’t know yet how to predict who is going to respond well to CAR T. We also don’t know who is going to get quite toxic from CAR T. These things are not yet predictable, although they’re working on it.

The other thing is, except really for a handful—and I’m talking a couple of patients—we don’t have much data beyond 2 years out. The bulk of people have been treated in the last 2 years, so the 2-year data is encouraging. And there’s a handful of patients who are 5, 6, 7 years out that are doing well, but I wish there were hundreds of patients and I wish they were 30 years out and I could see that data. That’s another issue.

When you enter CAR T therapy, there’s this ironic twist, and that is you’re hoping that you’re going to get sick. Because the sickness means that when these CAR Ts, which have been re-engineered to attack your cancer—they’re serial killers—they’re going in and killing off your cancer cells. And you get pretty darn sick when all this killing is going on in your bone marrow and in your blood and your lymph nodes are shrinking and your spleen. And this is called cytokine release syndrome. Cytokines are these enzymes that are released when there’s an inflammatory process going on, and it’s like the worst flu that you ever had, and most people need to be hospitalized for this. And you’re kind of hoping that you get it, but not get it too bad, because if you don’t get it—that doesn’t mean the CAR Ts aren’t working, but generally you have to a little bit of the cytokine release to get the benefit of the CAR Ts.

It’s very strange to get a therapy that you hope you get sick with because that means that it’s working. Having said that, and I was extraordinarily sick, I had a really bad time, but I got what I came for. When I was restaged, this cancer, which was 60% of my bone marrow, was gone to the best testing of something called MRD undetectable, or minimal residual disease undetectable, down to 1 in 100,000 or maybe 1 in 1 million cells. They could not find it anywhere in my blood or my bone marrow.