Dr Ian Flinn: Venetoclax, BTK Inhibitor Combination May Induce Greater Remission in Patients With CLL

SEQUOIA arm D study results show better outcomes are possible for patients with 17p-deletion CLL, explained Ian Flinn, MD, PhD, director of lymphoma research at Sarah Cannon Research Institute.

SEQUOIA arm D study results show better outcomes are possible for patients with 17p-deletion chronic lymphocytic leukemia (CLL); progression-free survival, response rate, overall survival all improved following administration of zanubrutinib plus venetoclax, explained Ian Flinn, MD, PhD, director of lymphoma research at Sarah Cannon Research Institute and director of the Sarah Cannon Center for Blood Cancer at Tennessee Oncology in Nashville.

Transcript

Why is arm D of the SEQUOIA trial, studying zanubrutinib and venetoclax in patients with treatment-naïve CLL or SLL and 17p deletion, so important?

In the SEQUOIA study, in this new arm D, we're looking at patients with previously untreated CLL who have a 17p deletion. In this way, by way of background, we know that, unfortunately in the area of chemo-immunotherapy in CLL, patients with 17p deletion had very poor outcomes. As a consequence, we really shouldn't be using chemo-immunotherapy any longer in the era of these targeted agents.

The first agent that was developed was ibrutinib, and we know that patients who receive ibrutinib or other BTK [Bruton’s tyrosine kinase] inhibitors have a much better outlook. Their progression-free survival, the response rates, the overall survival have dramatically improved with the use of a BTK inhibitor.

But still if you look at the BTK inhibitor use in 17p-deleted [disease] vs other subsets of CLL, the outcome is still inferior. As a consequence, perhaps combining these targeted agents, such as venetoclax, with a BTK inhibitor—in this case, zanubrutinib—we may get a deeper remission that improves progression-free survival and ultimate overall survival for this subgroup.

Again, we know it's much better with these targeted agents, but it's still inferior to when given as a single agent. Perhaps then a combination will improve the outcome for these patients.