ASH 2021 | Anti-CD20/19 CAR-T cell therapy in r/r B-cell malignancies

This trial was a follow up study to one that was previously published in Nature in 2020. And in that prior study, we used different manufacturing schema to produce the CAR T-cells. Identifying the weaknesses in that process, we developed a new study using IL-7 and IL-15 to expand the CAR T-cells, thinking that this more robust combination could improve the manufacturing parameters that ultimately improve clinical outcomes. So we used this combination to number one, shorten down the manufacturing length. And so we looked at different lengths of manufacturing, looking at an 8 day process and a 12 day process. Overall, we found that the manufacturing characteristics for this product were superior. We were able to achieve dose in a lower period of time, which is always important with a therapy like CAR T where timeliness is very important.

We continue to do a fresh infusion because we have a point of care production model, so we don’t cryo preserve the CAR T-cells before administration. And then overall, the toxicity and safety profile of this was in line with our previously published study with low rates of grade three to four cytokine release syndrome and neurotoxicity. And the overall outcome at the day 28 time point showed a high overall response rate for patients who are treated, and durability was seen in a subset of patients, just like other CARs where we did have patients who obviously relapsed disease. We had a single-Phase II arm in mantle cell lymphoma, which looked incredibly impressive. We have no relapses to date with the median follow up of 10 months. There was only one event, which was a patient who did have a non-relapse mortality due to gram negative broad sepsis. All of this work is being validated in an ongoing Phase II clinical trial, which is a multicenter trial of this same product using this manufacturing process in patients with relapsed/refractory diffuse large B-cell lymphoma.