SOHO 2025 | Five-year analysis of the ZUMA-3 trial: the efficacy of brexu-cel in R/R B-ALL

So I can do even better than describing the three-year analysis. So we presented our five-year analysis at EHA this past June and it’s outstanding. What do I mean by that? We’re talking about a median survival that hasn’t been reached for those patients who achieved complete remission. It’s better than we’ve ever done ever in ALL. And so when I step back and I think about it, when we started as a CAR T-cell process, the expectation for survival was somewhere around two to three percent. That’s what we started with. We knew from chemotherapy, we weren’t going to do better than that based on large retrospective series that had been generated as well as a series from MD Anderson. We weren’t going to get better than that. Why? Because we were coming in third, fourth, fifth, sixth, seventh line plus, right? We were really talking about heavily relapsed refractory ALLs that were coming in with blast burdens of 70%, really tough patients. So we went in saying, okay, well, this is where we’re at with chemo. With idel and blina, maybe a little better, 10%, 20% long-term. Okay. You know, this is what we got to beat. We’re five years out and again if we take the whole cohort, things around 40% survival, we take those in CR, it’s like 50-60% something, long-term survival. Blew me away, what on earth, how do we make sense of that, right? And this is where I have to speculate, this is where I have to guess. I get excited. You can probably tell. But why would giving a CAR, especially if we still see relapses, because we did, enhance our survival output to that degree? Are we doing more than we think we are by targeting the leukemia? We know that when we look specifically at post-CAR outcomes, they look really, they’re tough. They’re tough patients to treat. But I want to try and now create some nuance around that idea. There are those patients who progressed quickly, three, six months, probably weren’t even responsive to the CAR, right? They had lots of residual leukemia. If we’d looked like these more sensitive NGS techniques, we might have seen it. And then there are those who get much longer remissions, actually the surprising majority of patients who are now, yes, it came back, but it came back at nine months, a year, year and a half. Did we reset the biology somehow? Are we seeing something different that we need to account for that could explain these extended remissions? These weren’t easy patients, I can tell you, because I took care of the bulk of them on that trial. These were tough patients, and yet we have this incredible survival output. In terms of digging a little deeper, why did patients progress after CAR-T, especially those early progressors? It was clear that they didn’t have the same measure of expansion. We could show that by, we use a digital droplet PCR, but we convert it to a kind of a flow metric to give an idea of how many cells per microliter we need to see. And so we put that in our three-year manuscript. I think we’re developing the five-year manuscript now to kind of really build on that story and talk a little bit about other sort of factors that might have influenced outcome, hematotox and a few other features here. But I think the big picture is it worked and it worked better than I could have imagined and I’m excited to be able to share that again today. I hope the folks who are watching will check out, will go back and look at our EHA five-year data output because it’s really something incredible.

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