Differentiating among CAR T Products for Multiple Myeloma

Keith Stewart, MB, ChB: Peter, do you see any difference between them that strikes you that is worth calling out at this point? Or are they all still too early to see?

Peter Voorhees, MD: It’s too early to know. The overall response rates in all of them are obviously quite high. Depth of response is quite good. Median duration of follow-up remains quite short, and it’s important to recognize that this depth of response in a lot of these patients continues to deepen over time. I have [treated] patients for 1 to 2 years who are finally getting into complete remission. We have to wait in order to see any meaningful differences between the products.

Keith Stewart, MB, ChB: Natalie, what’s your experience?

Natalie S. Callander, MD: I agree with what Noopur [Raje] and Pete have said. One issue that has come up in our experience is that the manufacturing time can be daunting for patients. That doesn’t sound like a long time, 3 or 4 weeks. But there is this issue of patients falling apart during that interim and you are unable to get them to transplant. A lot of the trials are restrictive in what you can give patients, unfortunately. I’m not sure it makes a big difference what you’re trying to do in terms of this bridging. We should try anything. But that’s still a hurdle. Going back to other BCMA [B-cell maturation antigen]–targeted therapies, that is a disadvantage, that you just cannot immediately give it to an ill patient.

Keith Stewart, MB, ChB: Tom, where are we going to use these?

Thomas G. Martin, MD: We’ve been lucky at UCSF [Helen Diller Family Comprehensive Cancer Center] because we’ve had all the products in clinical trial. I agree with everybody that there’s no real difference at the current time. We’ve been very excited over the overall response rate. But a couple of limitations: 1, patients must come to the licensed cellular therapies place, like the transplant center. And that’s going to be a problem for a lot of patients. This isn’t going to be for everybody, unfortunately. It’s probably going to be less than half the people who are going to be referred for CAR [chimeric antigen receptor] T-cell therapy because they have to come into the transplant center.

Then we’re all excited about the response rate. But the disappointment is, for most people, the relapsing. Relapses continue to occur 1 year down the road, 2 years down the road, 3 years down the road. That’s a stark contrast to lymphoma, where if they’re in remission for 6 months, they tend to be in remission forever, which is troublesome. I wonder what the advisers think. For me, the problem is, are these guys all going to need maintenance after the CAR? We just haven’t addressed that situation at the current time. They’re going to need something else other than just a CAR.

Keith Stewart, MB, ChB: In fairness to the products, these are the worst of the worst patients in terms of the number of prior therapies and what their natural history would be. To me it’s quite miraculous that some of these patients pick up their bed and walk and have their first complete remission that lasts, even if it lasts for only a year, it’s often better than what the alternative was going to be.

Natalie S. Callander, MD: One of the most exciting things that we’re all going to be dealing with is, what about re-treating people with a different BCMA-targeted therapy. We use a drug conjugate after a CAR T, or can you use a BiTE [bispecific T-cell engager] before a CAR T? A lot of the trials are set up, so answering those questions now is quite limited. But we’re all going to try that. There are persuasive data that BCMA could be downregulated at the time of a CAR T relapse but comes back very quickly, particularly in people who have quite proliferative myeloma.

Transcript edited for clarity.