ASH 2022 | Safety and efficacy of CD7-targeted CAR-T therapy in patients with R/R T-ALL and T-LBL

When we submitted our abstract, at the time we had 53 patients, now we have 60 patients. So today I presented 60 patients with T-ALL/LBL treated with anti-CD7 CAR-T therapy. So those patients, 35 of them belong to refractory/relapsed T-ALL patients, and 25 of them belong to the LBL patients. So the median age was 19 years old, from two to 47 years old. Median bone marrow blast was 4.4%, but can be as high as 88%. Some of the patients had quite a very high peripheral blast in their blast count, up to 30%. And the median prior lines of therapy was five. And quite a few patients, more than 50% of patients, even have extramedullary disease involvement, including nine patients had CNS leukemia, and 17 patientd had a localized bulky disease, and 11 patients had diffuse extramedullary disease involvement.

Also, up to 22% of patients who had a prior allo-transplantation and failed the transplantation, then pursued the CAR-T cell therapy. And 30% of those patients also belonged to the high risk group of ETP, and eight patients had complex cytogenetic abnormality, and six patients had [inaudible] infusion gene, six had a TP53 mutation. So those are all heavily pretreated patients. So we gave them single dose infusion of anti-CD7 CAR. This is made fresh from patient’s peripheral blood, and also could be made from their previous transplant donor. Each patient only needs one infusion at the D1 of the three dose level. So about half of the patients received lower dose, half of the patients received intermediate dose. Only one patient received a high dose, and our manufacture success rate is very high. Only one patient failed manufacture, 98% success rate.

So then we take a look at our day 28 complete evaluation, we take a look at the bone marrow. 51 out of 54 of those patients were actually able to achieve MRD negative CR/CRi. And the other six patients without bone marrow involvement at enrollment, and were also able to maintain progression-free then in the MRD negative status. For the 31 patients with extramedullary disease involvement… overall response was about 81%. And 58% of them can achieve a complete remission, and 23 able to achieve a partial remission.

In terms of our long-term results, we have a median follow-up about 221 days, up to more than 600 days. So the totals for the total 60 patients, the 18-month overall survival and the PFS are both very high, can be up to the 73% and 55%, respectively. And those patients actually had a complete remission. Then 36 out of 47 of them actually proceeded to consolidation allo-transplantation, and the other 11 patients, just the CAR-T treatment alone, without transplantation.

Then in the two groups, we compared the OS and progression-free survival, also significantly high in the group who received a consolidation allo-transplantation. The overall progression-free survival was 61 versus 30%, so significantly better. So for the 11 patients without consolidation allo-transplantation, six of them relapsed. However, three out of six of those patients, to start with, had a very aggressive disease, they were never able to make it to the transplant. The other five still maintain progression-free, up to 180 days, they were still in a disease-free status.

So this product, generally speaking, is safe and manageable. A majority of patients only experienced a grade one and two cytokine release syndrome. And only 10% of patient had a grade three that we call the CRS. Only two patients had a grade one neurotoxicity, and one patient had a grade four neurotoxicity.

Regarding the infection rate, we monitored from CAR-T infusion to the transplant, or to the last follow-up, and two patients had CMV reactivation, and three patients had an EBV infection, and two patients had a fungal infection. However, none of the patients died from those infections.

So in summary, this is a good product, and also when we look at the peak in-vivo expansion time, by either by qPCR or by flow cytometry, were around the day 15, and also able to persist well per PCR analysis. So the method to generate those anti-CD7 CAR-Ts is quite novel. Those CAR-T cells were actually manufactured by transducing bulk T-cells with anti-CD7 CAR, then subjecting them in a natural selection into the cell culture. So after cell culture, you can see the majority of those cells turn from CD7 positive CAR negative, to CD7 positive CAR negative, by flow cytometry analysis.

So when you take a look at further analysis, you can still see those CD7 proteins and the mRNA are still present in those cells. So that’s indicated, these are fratricide resistant and were achieved by CAR-mediated CD7 epitope masking, or by intracellular sequestration. So generally speaking in final summary, this is a very highly effective and safe product, and even with pre-heavily treated patients, for those patients with extramedullary disease involvement, and for those patients who relapsed from previous transplant. And I think this is entirely new, anti-CD7 CAR-T therapy really provided a hope for those refractory/relapsed T-LL/LBL patients, and also a hope to be cured.