ERIC 2024 | CAR T-cells and bispecific antibodies in the treatment of double refractory CLL

So I think as patients are living longer after BTK inhibitors and BCL2 inhibitor therapies like venetoclax, etc., we are now starting to see this population of patients who are failing BTK inhibitors and venetoclax-type treatments, and we don’t have the perfect answer for that group of patients yet. So we have pirtobrutinib, which works for some amount of time. We have BTK degraders, which are also continuous pills, which will work for a certain amount of time. But we feel like immunotherapy with CAR T-cells or bispecifics might be a longer term answer to the double refractory patients, if you will. So we did the trial on TRANSCEND CLL 004, which is a Phase I/II study of relapsed refractory CLL patients who have failed at least two prior lines of therapy. Everyone needed to have had prior BTK inhibitor therapy, but about 60, 70% of those patients had also failed prior venetoclax or BCL2 inhibitor therapy. And in this difficult to treat patient population, the median prior lines of therapy were five. And what we saw in this study was that these very refractory patients actually had about a 20% complete remission rate. So in this difficult to treat patient population of double refractory patients, the complete remission rate was 20% on the liso-cel study. And those patients have had a very long and durable progression-free survival now over time, median of two-year follow-up already. In fact, I have patients now five years out who have not relapsed and are on no maintenance, no continuous treatment etc which is golden for them. It is logistically difficult to get CAR T-cells you have to be at a specialized center you have to first manufacture you know your own CAR T-cell and then give it back to patients and while the CAR T-cell being manufactured patients might be progressing etc. So bispecific antibodies might be another very good treatment option that is up and coming. So they have epcoritamab data looks really good where they treated patients a certain amount of time initially and then once a month forever more, so to speak. And on that trial, the complete remission rates, it’s just 23 patients, unfortunately, a very small group of patients, but the complete remission rate on that bispecific antibody trial is about 33 to 40 percent. But what remains to be seen is how durable will these be. And whether if you combine it with things like pirtobrutinib or BTK degraders in the future, will you be able to shorten the amount of time people need to keep getting bispecific antibodies? So the beauty of CAR T-cells one and done with some toxicity, the beauty of bispecific antibodies is it’s more available, more easily given by other people. They don’t have to be at a specialized center for that. So I think these are the up and coming immunotherapies that look pretty promising in CLL.