Implications of the SEQUOIA Trial Results of Zanubrutinib/Venetoclax in CLL/SLL

Jennifer R. Brown, MD, PhD, discusses the implications of the SEQUOIA trial, which looked at the combination of zanubrutinib and venetoclax for the treatment of patients with treatment-naïve chronic lymphocytic leukemia or small lymphocytic lymphoma.

Jennifer R. Brown, MD, PhD, a medical oncologist, director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute, and professor of Medicine at Harvard Medical School, discusses the implications of the SEQUOIA trial (NCT03336333), which looked at the combination of zanubrutinib (Brukinsa) and venetoclax for the treatment of patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

According to Brown, these findings establish the safety of the combination and its preliminary efficacy. While there are other studies looking at other Bruton’s tyrosine kinase (BTK) inhibitors in combination with venetoclax, this is the first study looking at zanubrutinib in this space.

Durability of remission and progression-free survival are going to be important over time, according to Brown. Additionally, there are questions over whether patients with 17p-deletions should stop therapy, even if undetectable minimal residual disease (MRD) is achieved in order to avoid treatment resistance.

0:08 | I think the findings established that the combination of zanubrutinib and venetoclax is safe and preliminarily effective in terms of response rate. We have a lot of such data with ibrutinib/venetoclax, and there are studies pending that look at that with acalabrutinib/ venetoclax. So, those are the other 2 covalent BTK inhibitors in the CLL space. But these are the first data looking at zanubrutinib and venetoclax in terms of safety and efficacy. And so, they're very encouraging in that regard that this combination is safe and well tolerated and highly effective.

0:40 | What really is going to matter over time, of course, is the durability of remission and the progression-free survival. And one big question in the field right now for the 17p-deletion patients is whether it's reasonable to stop their therapy, even if they achieve undetectable MRD. And so, this study has very stringent stopping rules for achievement of undetectable MRD, which is good. And then it will be very interesting to see how the patients do if we can retreat them with zanubrutinib and venetoclax at subsequent relapse, which hopefully will be many years out, because that would be a real benefit potentially compared to staying on therapy. If relapse occurs on therapy, we know there'll be resistant, and we can't retreat them with the same regimen. So, those data are probably still a few years out with any of the drugs actually, we don't really have that information for ibrutinib/venetoclax yet either.