SOHO 2026 | DALY 2-EU crossover analysis: zamto-cel shows promise in older patients with R/R LBCL

Zamtocabtagene autoleucel is a next-generation CAR T-cell therapy and unlike the currently available CAR T-cell therapies that only target CD19, this CAR-T goes after two antigens, CD19 and CD20. And so this is some data that is based off the DALY 2-EU clinical trial. So in the European Union, they did a clinical trial where they randomized older patients to getting zamtocabtagene autoleucel as a second-line treatment to R-GemOx focused specifically on patients that were transplant ineligible. So thinking about your older patients, less fit for high-dose chemotherapy and stem cell transplant. And so the data here is looking at some of the correlative data, looking at the expansion kinetics and how that impacts clinical outcomes, and also looking at the crossover, because the study did allow crossover. And so some of the key findings of this data is really showing that how expansion can correlate with clinical outcomes. And we see good expansion in this older patient population, a worry that we have when we give immunotherapeutics in older patients. And then in the crossover, that you are able to save patients who progress on GemOx and give them, you know, zamtocabtagene autoleucel now as a third-line therapy. And so that’s important data to know that, yes, ideally, right, the primary results of the study showed that giving zamtocabtagene autoleucel as a second-line therapy was superior to R-GemOx. But for those patients who got R-GemOx, who then subsequently progressed, had similar outcomes to the patients who got zamtocabtagene earlier. And so sort of subset data from a larger clinical trial, but we think important in sort of talking about the zamto-cel story. And one of the key overall findings of zamto-cel in this clinical trial and other clinical trials is that so far, it seems that dual targeting of more than one antigen can maybe limit antigen escape. So we find that even when patients do relapse, they largely retain CD19 and CD20. Why is that important? Because we have drugs that can target that after CAR-T. And so this retention of target with dual targeting CAR is a really promising sort of mechanism that we’re learning more about.

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