Second Generation CLL Treatment: Zanubrutinib + Sonrotoclax | Constantine Tam, MD, MBBS | ASH 2023

Hi, I'm Professor Kon Tem. I'm a hematologist from Alfred Hospital in Melbourne, Australia, and I'm here at ASH 2023. I'm very lucky this year to have been invited to present our work on a second generation combination of two targeted tablets for CLL. So by way of background, your audience may be aware that there's a medication called ibrutinib and a medication called vitinoxalax, which are separately considered to be some of the best drugs possible in CLL. And even back as far as 2014, our group reported that if you combine ibrutinib and vitinoxalax together, then you get very good outcomes for treatments of CLL and other diseases. Now although that particular combination of ibrutinib and vitinoxalax has been successful, we felt that we can make it work better by using second generation drugs. And we also felt that the side effect profile of this combination can be made better by using second generation drugs. So my talk this year is to combine xenobutinib, which is a second generation version of ibrutinib, so the drug works better and has fewer side effects, with a drug called somrotoclax, which is a second generation version of vitinoxalax. And somrotoclax is better than vitinoxalax, and that is about 10 times stronger. So we did a trial where we basically treated 100 patients with CLL, and we gave them the second generation xenobutinib and the second generation drug somrotoclax together in combination. And we saw some really pleasing results. And in particular, we saw that the side effect profile is very benign, probably better than the first generation combination of ibrutinib and vitinoxalax. And we also saw very rapid destruction of leukemia, such that patients enter into a state which is called minimal residual disease negative, meaning that we can't find any cancer in the patient's body at all, at a much faster rate than the first generation combination. So we're optimistic that this second generation combination will be an even bigger improvement than the first generation combination is. At the moment, these drugs are still investigational, so you can't get them from your doctor. But we're looking ahead. We hope that in about five years or so that this will represent one of the best treatments available for CLL.