EHA 2025 | The durability of responses with CAR T-cell therapy in ALL and predictors of long-term remission

I think the updated data from the obe-cel especially, and then obviously the brexu-cel data has been out there for a longer period of time. And we do know that some of these patients, including our original data from our own CD19 CAR T-cell therapy work coming from our center at MSK, that we do. And I have patients who are beyond now 10 years after single infusion CAR T-cell therapy and able to maintain remission without the subsequent transplant. So we all have those patients. And there is definitely a potential for CAR T-cell therapy to generate that super durable responses and possibly a cure. I think the cure is definitely feasible and possible after CAR T-cell therapy. What obe-cel data has shown that for now with up to three years of a follow-up that about roughly about 40% of the patients are able to achieve that long-term remission. Brexu-cel also subset of the patients are able to do that. So I think the short answer is that we do know that it is possible that these patients are, the CAR T-cell therapy has a potential and has proven that it can serve as a definitive therapy. And a more difficult question is how do we know who these patients could be at the time of a treatment or even a month after? I think that’s the part that we do need more data, unfortunately. We do have some biomarkers, as we talked about, in patients who have a lower disease burden at the time of T-cell infusion. Patients who have a lower inflammatory score, such as CAR-Hematotox score, has shown to be better. We have shown that with the brexu-cel real-world data, patients who have a low CAR-Hematotox score at the time of T-cell infusion also tend to have a long-term survival, which tend to track with a lower disease burden, but not always. So I think that both biomarkers might be equally contributing, independently contributing to each other. So I think that this could serve, doesn’t guarantee, but at least hopefully guide us making the decisions with the patients, informed decisions about the potential benefits and risk of whether we’re to transplant or not after CAR T-cell therapy. The CAR T-cell persistence is a little bit tricky to interpret. I think it has shown to be an important biomarker for obe-cel, but that turned out not to be the case for brexu-cel. So that is dependent on which product that we use. But again, the CAR-T hematotox and the disease burden both have consistently come out to be a good prognostic marker for long-term survival. So those are kind of what we have now. But again, I think it’s encouraging with the longer data that we do have with both of these products, with the brexu-cel and obe-cel, the commercial ones, again, with our prior generations, that we’re not beginning to see long-term survivors after a single treatment of CAR T-cell therapy without transplant. So I think that is very encouraging news. And that paves the way to move this CAR T-cell therapy to earlier lines of a setting, even in the frontline setting, as some of us are investigating this product in that, that if it works so well and has the potential to cure in those relapsed/refractory patients, what could we achieve in the earlier lines of a setting in frontline disease where there are less treatment lines, and also lower disease burden? We think it might be the perfect setting to generate the most durable responses. So we’re hugely excited about the future clinical trials that are going to be conducted very soon in the near future to answer this question in frontline setting in adult patients with ALL.

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