GPRC5D Directed CAR T-Cell Therapy | University of Alabama | Susan Bal, MD | ASH 2023

So I'm Susan Baal from the University of Alabama at Birmingham. I was delighted on behalf of my co-investigators to share some of the results from BMS 986393. This is a potential first-in-class autologous GPRC5D-directed CAR T-cell. And we were able to share some of the updated results from this ongoing Phase I study. So at the data cutoff of September 2023, we now have infused 84 patients. And this is a group of pretty heavily pretreated patients with five prior lines of therapy. Patients have mostly high-risk disease, with 41% of patients having high-risk cytogenetics. There are 44% patients with extra medullary disease. And overall, 20% of the patients were even BCMA refractory. So what we saw is that this agent is associated with very good efficacy at the recommended Phase II dose, which was shared at this meeting of 150 million CAR T-cells. The response rates, that's patients who had at least a partial response or better, was about 91%, with about 48% of those patients having a complete response. So that's very encouraging in this heavily pretreated late-line population. In terms of the safety, this was felt to be very much within the realm of what we see for patients with relapsed myeloma. Most of the side effects were low blood cell counts, which is known with patients who get CAR T-cells in this late-line setting. We also saw CRS. But at the recommended Phase II dose, the exciting news is we didn't really see any grade III or higher CRS events. So most events were low-grade and manageable. We also saw a lower incidence of neurotoxicity, particularly serious neurotoxicity associated with ICANNs. But the main thing of note was in the study, we are seeing some non-ICANNs neurotoxicity events such as dizziness, ataxia, difficulty with speaking, which was seen in nine patients on our studies, about 11% of the population. And we're still better trying to understand what is causing these effects, what's associated with these effects. So far, it appears to be dose-related. And so far, with institutional treatments, there have been some signs of stability and reversibility. So we need to follow these toxicities on an ongoing basis. The good news is compared to T-cell redirection using T-cell engaging therapy, such as Telcoeta map, we see a lot of toxicities that affect the hairs, the skin, oral cavity, and nails. With this particular CAR T, given that it's a one-time treatment option for patients and it's not ongoing therapy, these toxicities are mostly transient, low-grade, and manageable. For example, 86% of the patients who had these side effects did not require treatment. Only about a quarter of patients had these to begin with, and they resolved at a median of about just under four weeks. So I think that is certainly encouraging data. And as we get more follow-up and study this in different situations, both in combination therapies and in a larger phase to study, I think we'll understand better the toxicity profile as well.