ASH 2023 | Liso-cel in R/R CLL: 24-month follow-up of TRANSCEND-CLL-004

This is a Phase I/II trial of liso-cel CAR T-cells in relapsed/refractory CLL patients. All patients needed to have had prior BTK inhibitor therapy and then 2 or 3 lines of total therapy, depending on their risk category of CLL. We concentrated on a subgroup of patients who have failed both BTK inhibitor therapy as well as venetoclax and then relapsed with their CLL. So, the median prior lines of therapy in our patient population in this study was five already. And these patients all received liso-cel. We treated 118 patients in this study. Out of that, about 88 patients were available for efficacy, and out of that, we concentrated on the double refractory patient population, as I said earlier. So, about 50 patients was the primary efficacy analysis subset of patients. We met our primary endpoint which was complete remission rate at now 20% actually, which is very good for a patient population that has failed a lot of novel therapies already. And then our overall response rate was 44%. We actually saw a lot of undetectable minimal residual disease cases as well in this difficult to treat patient population, about 60% in the blood and marrow.

And the treatments were fairly well tolerated. We saw no grade four cytokine release syndrome, there were about 8% grade three cytokine release syndrome. There were about 18% neurotoxicity events at grade three, one grade four, but pretty much everybody recovered with the usual treatments of tocilizumab and steroids. 

And what we saw in the long term, now that I presented the two-year follow-up, or the two-year update of median follow-up, we saw a median duration of response of about 35 months, which for a double refractory patient population is, we think, very good. We also saw that the patients who achieved complete remission, the 20% that had achieved complete remission, the median duration of response has not been reached, median progression-free survival has not been reached, median overall survival has not been reached. So those patients are doing very well for a longer period of time. Even the partial remission patients, their median duration of response and their median progression-free survival is very respectable and good, almost a couple of years, and I think we need to just follow these patients longer and see how they do over a long period of time. But the bottom line is it’s one treatment of CAR T-cells, and now people are going two/three years without relapsing, which gives them a lot of clinical benefit where they don’t have to be continuously on pills, suffer side effects, frequent doctor’s visits and things like that. So we think it’s a very good treatment option for, especially double refractory, relapsed CLL patients.