ASH 2024 | First results of CAR-PRISM: early safety and efficacy of CAR-T in high-risk smoldering myeloma

So the CAR-PRISM trial is looking at use of ciltacabtagene autoleucel, which is an anti-BCMA CAR T-cell therapy in patients with high-risk smoldering myeloma. So patients with high-risk smoldering myeloma have a high risk of progression to symptomatic disease in the next two years, and there have been numerous interventions that have been studied in this population to try to delay time to progression. At this meeting, we’re seeing the results from the daratumumab study showing benefit over observation in that patient population. So the next question is, how can we make that even better? Because in that study, the response rate was about 60%, and about 40% of patients still relapse at five years. 

So we looked at different strategies and how to intervene with either more combination therapies that are myeloma-like in this population, and now looking at the first time, CAR T-cell therapy, because these patients have a much more fit immune system. Can you actually give them a one-time CAR T-cell infusion and maybe prevent the disease from developing, perhaps in their lifetime. So the CAR-PRISM trial is looking at ciltacabtagene autoleucel for these patients with high-risk smoldering myeloma. This is the report of the first six patients treated on this trial, which is part of the safety run-in. We studied two different doses. We studied a 0.5 dose and a 0.75 dose, which is the standard dose for CAR-T cell therapy for ciltacabtagene autoleucel. 

There were no dose-limiting toxicities noted in either of those two dosing cohorts and the expansion phase of the trial i’s currently ongoing. Patients had expected toxicities with this CAR T-cell product. We did see CRS but no grade 3 or greater CRS was observed in this trial. There were some cytopenias that we expect from lymphodepletion in the CAR products but those were all transient and no delayed or persistent cytopenias were observed. At this time we had one patient in the part of the safety running that developed the transient Bell’s palsy that resolved within two weeks. And again, these are some of the side effects from these therapies that we know about with CAR T-cells, particularly with ciltacabtagene autoleucel. But the great news is that all patients responded to therapy and they all had a complete response and all were MRD negative at 10 to the minus 6. And the first three patients are now a year out. So they have sustained MRD negativity at that one-year mark with the one-time use of ciltacabtagene autoleucel infusion. And the remainder of patients also remain MRD negative at their last follow-up. And there have been no patients that have progressed to overt myeloma at this time. So, so far, we’ve seen encouraging results from the safety run-in. And, you know, we hope to update the results at future meetings with this approach.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.