Combination of zanubrutinib and venetoclax shows promise in high-risk TN CLL/SLL with del(17p) and/or TP53 mutation

Dr Alessandra Tedeschi - Niguarda Cancer Center, Milan, Italy

This is a combination study of zanubrutinib with venetoclax; it’s the SEQUOIA Arm D,  SEQUOIA is a big study addressed to treatment naïve patients. In this case zanubrutinib was used in combination with venetoclax and in this part of the trial we are addressing the efficacy and safety on 17p deleted patients.

What was the study design?

The two drugs have been given in combination, first a lead-in with zanubrutinib followed by venetoclax. Zanubrutinib could be discontinued after 16 cycles and zanubrutinb could be continued until MRD undetectable disease.

What were the results of this study?

The combination showed to be very effective in this high-risk population of 17p deleted patients. It should be highlighted that they were not only 17p deleted but there was one third of the population characterised of complex karyotype. A high response rate, 100% response rate, with a prolonged progression free survival at this point at 24 months of about 95%.

What is the significance of these results?

The results are very important because we are dealing with a very high-risk population with a high risk not only, as I said, 17p deletion but also complex karyotype. This population is a very difficult to treat population and with this combination we saw a prolonged progression free survival and the combination showed to be safe in our hands. So it’s an invaluable option for our patients.

What is next for this study?

The next part of the study is to see how the same combination of zanubrutinib and venetoclax performs in patients that are not so high risk by prognostic disease features. The study is still going on and in the future I believe this combination will be an available option, fixed duration treatment for our treatment naïve patients.