EHA 2021 | Early safety and efficacy data of AUTO1 in R/R indolent B-cell lymphoma

Essentially, AUTO1, we have discussed this before, it’s the fast off-rate CD19 CAR that we’ve been using at UCL in the context of adult and pediatric acute lymphoblastic leukemia. The profile of this CAR is it it’s a sort of a low toxicity and high persistence CAR, so it’s lent itself really nicely to leukemia. But we thought it was those features that made it particularly attractive to extend the remit and to look at it in other types of lymphomas. So indolent lymphomas, high-grade B-cell lymphomas and CLL. Because of course these are older patients with lots of co-morbidities and so on, and would benefit from a potentially a low-tox CAR option.

So essentially, to date, we’ve actually, we’ve recruited 13 patients into this extended cohort and of those 13 patients we’ve actually managed to treat nine so far. And these are all patients, the patients that we’ve treated so far, are all from the indolent non-Hodgkin’s lymphoma cohort. So we’ve got, of those nine, the majority are follicular lymphoma patients, but we have a couple of mantle cell lymphoma patients in there as well.

And these patients, they’re actually on the older side. So, the median age is 56. The oldest patient we’ve actually treated is 68, they’ve been heavily pretreated. They’ve had a median of three prior lines. Almost 50% of them have had an autograft. They all have high-stage disease when they came in. Stage three/four disease in all of them. And all of them required bridging. But actually, despite that, the fairly kind of, I guess, high-risk patient profile, we managed to manufacture for all of them, which was great. That’s using our sort of semi-automated closed process. All of the products were, they reached release criteria, they were enriched like we described previously with central memory populations, which are associated with nice long persistence and limited T-cell exhaustion. So that was all, we were really encouraged by that.

And then when we infused the CARs, actually what we got was really nice engraftment. So, we got engraftment that’s probably comparable to what we’ve seen in the leukemia cohorts, which is good. So, sort of peak engraftment round about day 14. And we also saw really nice persistence of the CARs to date. We’ve got the sort of follow-up beyond six months for some of the patients with ongoing CAR T-cell expression in those patients. And the nice thing about this is that the CAR actually behaved as we sort of expected it to with minimal immuno-toxicity. So that was really encouraging. Even in these older patients with high disease burdens, we essentially, we only saw one grade two CRS out of the whole cohort of nine and no grade three CRS. And we actually saw no ICANS at all in this population. So, that was also really encouraging for us.

And in terms of the actual responses. Out of those infused patients, all of them managed to achieve a complete metabolic response by Lugano criteria by three months. So, we had a hundred percent response rate essentially in this population. So again, that’s great. I mean, these patients are coming in with lots of disease, very well-tolerated CAR, straightforward manufacture, good engraftment, nice persistence. So, you know for us this is really hugely encouraging.

Now in terms of the, sort of, durability of the response. So, out of those infused patients, there was one who did relapse at six months. But it was quite a limited stage relapse under the skin, beside the knee. So, that patient has gone on to have radiotherapy for that. I guess, I mean, he’s a specific case in the sense he’s the only patient in our cohort who had had a prior allograft and an autograft and had failed ibrutinib, and so was a particularly high-risk patient, so I guess his disease was fairly aggressive. And there was one other patient who sadly he died at six months of COVID-19 whilst in remission.

So again, I mean, we ran this study the whole way through the COVID pandemic. So, it was really a very challenging thing to do, keeping all those patients safe. And unfortunately, he didn’t manage to avoid COVID. So, that was being casualty for this study.

So, that would sort of summarize where we’re at today with our, that’s with our indolent lymphoma cohort. In the meantime, the data is not necessarily reported in the poster, but we continue to recruit the DLBCL. We continue to recruit CLL and we’re very keen to see whether we’re seeing sort of comparable responses and toxicity profiles in those cohorts. Because again, you know this is AUTO1 with its unique binding kinetic. It just seems to hold certainly intellectual advantages over some other binders in the B-cell cancer space. That really probably summarizes that that poster for you today.