Peter Voorhees, MD: I want to talk about 2 phase 3 studies that have recently been published in the New England Journal of Medicine. The first one that came out was KarMMa-3 [NCT03651128]. This was a study that looked at ide-cel [idecabtagene vicleucel] vs standard-of-care therapy, and there are 5 different regimens that they could choose from, for patients with myeloma who relapsed earlier. Specifically, they had to have had at least 2 prior lines of therapy, they had to be lenalidomide refractory, and they had to have been exposed to prior daratumumab. Since most people do not discontinue daratumumab because of toxicity, because it stops working eventually, most of the patients in the study not only were lenalidomide refractory, they were also daratumumab refractory, and a good proportion of them were also proteasome inhibitor refractory as well. With all of that in mind, this particular study demonstrated a strong PFS [progression-free survival] advantage with the use of ide-cel over standard-of-care therapy. The standard-of-care therapy had a median progression-free survival of about 4 and a half months or so. For those who got ide-cel, it was about 13 and a half months. We’ve got that dataset out there.

We now have a more recent set of data from CARTITUDE-4 [NCT04181827], and this was the topic at the [American Society of Clinical Oncology] meeting in the plenary session at [European Hematology Association]. This was a study that looked at cilta-cel [ciltacabtagene autoleucel] vs standard of care. The 2 standard-of-care regimens were daratumumab-pomalidomide-dexamethasone, and pomalidomide-bortezomib-dexamethasone. You could choose one or the other and you were randomly assigned again to cilta-cel or one of these 2 strategies. In this particular study, they showed that the response rates were better with cilta-cel, the depth of response was better, just like it was with ide-cel. The progression-free survival was about 12 months for those who got standard-of-care therapy, and it had not been reached for those who got cilta-cel, and the hazard ratio for PFS in this particular trial was on the order of the high 0.2 range, so it was more than a 70% reduction in the risk of progression or death, which really garnered a lot of attention. What are your thoughts about those datasets and how we might see CAR T-cell therapy being used in the future?

Amy Soni, MD: Impressive data, certainly. I don’t have personal experience with it, but I wonder about using it earlier in the course of myeloma treatment.

Peter Voorhees, MD: One of the things that you often hear people talk about, not just with CAR T-cell therapy but with any new treatment, they’re hesitant to use it earlier because they want to be able to save it for relapse. What am I going to use when this patient relapses after CAR T-cell therapy? What are your thoughts about that? Save it in reserves? Or if the FDA likes what they see, we get an approval for ide-cel in patients with 2 or more prior lines of therapy, we get an approval for cilta-cel with 1 to 3 prior lines of therapy, are you going to gravitate to using these agents earlier or are you going to save them for later?

Reed Friend, MD: I think it’d be very appealing to use it earlier as long as we have bed availability. If it were a perfect world, then I think putting it earlier in the treatment algorithm is something that we should do.

Peter Voorhees, MD: I would agree with that for a couple of reasons. You know, we’ve already talked about the logistical challenges of CAR T-cell therapy in the heavily pretreated patient population. This is a group of patients who may not have good drugs to control their disease before they get apheresis for CAR T-cell therapy. They may not have adequate therapies for bridging treatment to control their disease. Just in our experience, the larger the burden of disease going into a CAR T-cell infusion, the worse the adverse effects are going to be, the more severe and protracted the cytokine release syndrome is going to be, the higher the likelihood of neurologic adverse effects, the higher likelihood of cytopenias and more prolonged cytopenias. With that comes the risk of infection. When you’ve got drugs available to control the disease, both before apheresis and during the manufacturing process, and the burden of disease is low going into CAR T-cell infusion, it is so much easier for the patients. In the early relapse space, we’ll have drugs that we can use to manage the disease while we’re getting them scheduled for apheresis while we’re in the process of manufacturing those cells. I personally think that if the indication changes for both of these products, that will be a game changer, with the caveat being that there are going to be more patients who are going to be eligible for these products and so there are going to be access issues not from just a manufacturing perspective but also just from a center perspective. We’re going to have to hire more people in order to be able to treat all of these patients.

Transcript is AI-generated and edited for clarity and readability.