CAR-T Meeting 2026 | Zamtocabtagene autoleucel, a tandem CD20-CD19 CAR, in R/R LBCL: data from the DALY 2-EU study

So, the DALY 2-EU trial was first presented at ASH 2022 by Dr. Peter Borchmann. He presented the first results in terms of efficacy and toxicity of this trial. This trial, for context, is a randomized clinical trial in the second-line setting for transplant non-eligible large B-cell lymphoma patients comparing a CAR-T construct, dual CD19/CD20-directed CAR-T, zamto-cel, with standard of care, you know, chemoimmunotherapy, R-GemOx. So I think it’s worth mentioning this is the first trial, which is randomized in transplant non-eligible setting, including a CAR T-cell construct. And primary endpoint of event-free survival was met in favor of the zamto-cel arm compared with R-GemOx. So that was presented at ASH. 

In this EU CAR-T meeting, what we presented was data in terms of PK/PD, so CAR T-cell expansion data of this specific dual-targeted tandem second-generation 4-1BB co-stimulatory domain construct. In this trial, what we observed was in line with other CAR-T constructs we’ve seen, such as axicabtagene ciloleucel. We observed that the peak CAR-T cell expansion was associated with achieving a complete response, so it was associated with efficacy. And I think, interestingly, it was associated specifically with those patients achieving a durable CR. So if we looked at patients achieving a CR and patients who did not achieve a CR, significantly higher peak CAR T-cell expansion in the CR group. But if we worked further on this comparison and separated those patients into three groups, so patients who achieved the durable CR, patients who achieved the CR and relapsed, and patients who never achieved the CR, we observed that the higher peak CAR T-cell expansion was specifically focused in the durable CR patients. Patients who achieved the CR unfortunately relapsed at a similar peak CAR T-cell expansion to those patients who never achieved the CR. So it definitely seems that the peak CAR T-cell expansion, you know, is playing a key role in terms of efficacy with the zamto-cel. 

Persistence, that was also correlated with a higher chance of achieving a durable remission in patients who had been infused with zamto-cel. And when we looked at tumor burden, this, you know, as with other products, also seems to play a role. Patients with a higher tumor burden were less likely to achieve a durable remission with the CAR T-cell treatment. But interestingly, when we kind of compared, you know, the impact of CAR T-cell expansion and tumor burden, it did seem that CAR T-cell expansion was kind of, let’s say, the key player here. You know, there was a high peak CAR T-cell expansion above the median. This seemed to be able to overcome, in many cases, the higher tumor burden that some patients had before entering the trial. 

So kind of in conclusion, you know, the primary results of efficacy and toxicity of this trial were presented at ASH. In this meeting, we, you know, presented further data specifically focused on PK/PD, CAR T-cell expansion, and persistence, kind of supporting the same results we’ve seen with axi-cel and other constructs, confirming peak CAR T-cell expansion, in this case also persistence, are very important for the efficacy of the specific product.

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