Next-Generation Regimens for Multiple Myeloma - Episode 11

The Promise of Anti-BCMA CAR T-Cell Therapy in MM


A. Keith Stewart, MB, ChB: So, let’s talk about probably the most exciting field in myeloma right now, which is immunotherapy, particularly active cellular immunotherapy. But BCMA as a target has emerged. Ed, your center has been at the forefront of CAR T-cell therapy. Tell us a little bit about where are we at. Let’s start there.

Edward A. Stadtmauer, MD: Well, CAR T-cell therapy has been the most exciting explosion on the radar of therapy.

A. Keith Stewart, MB, ChB: Overnight?

Edward A. Stadtmauer, MD: We realize that these studies that really started with cellular immunotherapy are about 20 years old. So, it seems like it’s brand new, but actually, is it overhyped? Well, there’s no question that the patients who were dying of the disease and who received these therapies that they were treated with are now doing well long term. So, that’s exciting and remarkable. Whether it is THE cure for everyone with myeloma is still something that needs to be worked on. The way I see it is we have proof of principle. These therapies are definitely working, but now it’s an engineering problem where we have to engineer these cells in a way that will be more broadly applicable and lead to long-term cures for patients.

A. Keith Stewart, MB, ChB: That is a good introduction. Yesterday at this meeting, we heard some very specific data on one of the compounds from Bluebird and Celgene called bb2121. Dr. Chari, what do you think of that? I think maybe for the audience just recap what we were shown.

Ajai Chari, MD: So, the bb2121 was a study with very heavily pretreated patients, median of 7 lines of prior therapy, and, I think as Tom alluded to, up to 23 was the upper limit of the range. So, in this heavily pretreated population, there was a very rapid response rate of nearly 100%. And I think what we learned new this time is really the PFS, which we really didn’t have. And the PFS was around 11.7 months, I think.

So, I think what that tells us is, first, this is an amazing result for such a heavily pretreated population, that the response rate and the PFS are superior to all other drugs that have typically been tested in this heavily pretreated population. I think the one caveat is the nitty-gritty of how patients get on to the study. So, you need to meet progression criteria when you sign consent, but from that point to the administration of CAR T, the manufacturing process, it’s anywhere from 4 to 6 weeks. And although you’re allowed bridging therapy, who you’re going to allow to sign consent is one, selection bias, and then a second is who can actually make it to the 4 to 6 weeks. But putting that aside, undoubtedly very impressive results.

A. Keith Stewart, MB, ChB: Tom, what do you think?

Thomas Martin, MD: No doubt, the patients who were enrolled in this trial were the worst of the worst. They failed proteasome inhibitors, they failed IMiDs.

A. Keith Stewart, MB, ChB: Their disease was the worst of the worst.

Thomas Martin, MD: Yes, exactly. They were very wonderful, and failed daratumumab. And so, for these patients, we did not have real therapeutic options for them. And despite that, the response rate was tremendous. People say that the progression-free survival of 12 months, is it long enough? And they receive the CAR T-cell therapy and then they received no other therapy, half of them, for 12 months. If we could do that with other therapies, we would choose that therapy in a second to be a one-and-done type therapy for a year. I think this has dramatic implications, especially as in these end-line patients, so now we have to move it closer to early relapse, frontline.

A. Keith Stewart, MB, ChB: I think maybe there was a little bit of deflation with the PFS, because I think there had been this notion that, like the acute leukemia children, this was going to be a one-shot cure. That’s probably not the case. If you treat people at this stage of the disease, some will likely be cured, but there are others who are relapsing.

Ajai Chari, MD: That issue is also relating to the engineering that Ed mentioned, which there was one neurotoxicity early that subsequently has not been seen again with the lower dosing. So, I think we really need to learn better about the dosing of the cells and the vector copies.

Amrita Krishnan, MD, FACP: But I think also Harry gave a talk and he mentioned a patient who, at first CR, asked, “When can I get CAR T?” To speak to the toxicity as well and the early experience in CAR T cells is important.

Transcript Edited for Clarity