ASH 2023 | Var-cel shows promise for the treatment of CLL and Richter’s transformation

Patients with CLL have a very good prognosis, but once these patients are relapsed or refractory to modern targeted therapy, like BTK inhibitors, they have very bad outcomes and even worse prognosis [is seen in those] CLL patients who have transformation into Richter’s syndrome. Again, these patients have a chance of achieving CR of around 20% with conventional immunotherapy, so, they are all patients with an unmet medical need. 

So here’s where we are trying to provide CAR T-cell therapy to these patients and we have been treating patients with our own locally manufactured academic CAR T-cell, which is varnimcabtagene autoleucel or ARI-0001 cells. And the truth is we have been treating a small amount of patients, around 20 patients, all of them were very high-risk patients for cytogenetics, CLL-IPI, tumor burden. 

And the question is, does CAR-T work in CLL and Richter’s transformation and in a comparable way to other commercial CAR T-cells in approved indications. So there’s this fear that CAR T-cells don’t work as good in patients with CLL because of the well known T-cell dysfunction that characterizes these patients. But the truth is, we have been treating these patients, and we have seen a safety profile that seems to remain in line. We have seen a rate of 90% of all grade CRS, but it has been severe in only 11% of patients. And as for ICANS, we only have seen mild ICANS in 11 patients and no severe cases and again, no treatment-related mortality. 

And as for efficacy, which is the most important part, we have seen an overall response rate in the CLL compound of around 90%, being MRD-negative in 80% of patients. And for the patients who had Richter’s, we also saw an overall response rate of around 80% and a complete response rate of around 60%. So overall, we have been seeing in these patients with CLL, with or without Richter’s, a 60% complete response rate. And the most shocking part of this is that most of the patients that achieve complete remission don’t seem to be relapsing. So the hardest part is to achieve remission, but the ones to achieve remission have a progression-free survival of around 3.7 years. So it’s encouraging to us to see that the quality and the rates of response seem to be in line with the ones we have been seeing in other malignancies.