ASH 2022 | Evaluating dual-targeting CD19/22 CAR-T cells in patients with R/R ALL

So, one of the biggest problems that we had with our CARPALL study when we were delivering just the CD19-targeted therapy, which is called AUTO1, when we delivered that therapy, we had excellent toxicity profile, excellent efficacy, but we had six out of 14 patients relapsed and five of those had a CD19 negative leukemic escape. And none of those patients survive long term. So this really is a devastating outcome and other real-world data from the use of licensed CAR-T cell therapy has demonstrated the same outcome for those patients that have leukemic escape by this mechanism.

So we were very keen to try and deliver a dual CAR approach because there’s some potential to reduce this ability of the leukemia to escape if you’re targeting two antigens at the same time. And we had a very unique way of delivering that through a cotransduction approach. So actually the patients had three different CAR-T cell populations given back to them. They had a CD19 single CAR population, a single 22 CAR population, and they had a dual CAR population. And then we were able to track these populations over time and understand the outcomes for the patients.

So it’s a median follow-up of 8.7 months. We’ve demonstrated that there have been no relapses or emergence of measurable residual disease, which is related to antigen negative escape. So this is unique, again, a sort of unique outcome in the field. It’s still an early timepoint, but it’s very relevant for CD19 negative escape because that tends to happen within the first sort of six months, six to nine months. So we are really encouraged by that data.

And now we’re looking at ways to try and really optimize even further the quality of our product because we found that in treating a heavily pre-treated cohort of patients, so four of them had failed prior licensed CAR-T cell therapy, these were really advanced patients who’d had multiple, multiple lines of immune therapies even before coming to our CAR-T product. And we know that patients that have failed prior CAR-T have a lower response rate when they then come to the current, to the next CAR-T cell therapy that they have. But we were able to demonstrate our response rate was 83% and those were all patients that received, well, attained an MRD negative complete remission. So that was 83%, 10 out of 12 patients.

And in addition, we had an event-free survival, which was basically exactly the same as for the ELIANA study. So we had a 60% event-free survival, which is really encouraging in this heavily pretreated cohort of patients. We also worked really, really hard in selecting our CD22 CAR, and that was with our collaborators at Autolus. And that was very important because we demonstrated a really great expansion of the CD22 CAR expressing populations even in patients that didn’t have CD19 on their leukemia, showing that that CAR was really effective. So these data are really, really important in the field.

Unfortunately, we’ve had emergence of measurable residual disease or relapse in a total of five patients. So three have relapsed and two have had emergence of measurable residual disease. In all cases, this was expressing both CD19 and 22 and was related to a failure of persistence of CAR-T cells at the point that they had their relapse. So this is something that we are working on in terms of manufacturing processes and trying to improve the persistence so that we can just eliminate all of those causes of relapse if we possibly can. But we’ve had no antigen negative relapse to date. So that really is again, a sort of point of progress for the field.