Zanubrutinib/Venetoclax Shows Efficacy in High-Risk CLL Subgroup

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

The multiarm, randomized phase 3 trial evaluated the efficacy and safety of the next-generation Bruton’s tyrosine kinase inhibitor zanubrutinib in separate cohorts of patients with and without deletion 17p (del[17p]), which is linked to higher risk in CLL. Patients in the del(17p) arm received zanubrutinib followed by venetoclax until reaching disease progression, unacceptable toxicity, or undetectable minimum residual disease status.

According to Brown, interim results of 36 patients with del(17p) who received zanubrutinib were presented at the American Society of Hematology annual meeting in December 2021, out of approximately 80 planned patients that were enrolled. Of the 35 who were evaluable, 30 had a response, for an overall response rate (ORR) of 96.8% (95% CI, 69.7%-95.2%). The median follow-up was 11.2 months. A complete response (CR) was observed in 4 patients (12.9%).

Grade 3 or higher adverse events (AEs) were reported in 37.1% of patients. One patient left due to being diagnosed with lung cancer, 1 ended treatment due to localized disease progression, and another due to withdrawal of consent. All others remained on treatment, while others have yet to be evaluated by bone marrow biopsy, according to Brown.

TRANSCRIPTION:

0:08 | There were 36 patients evaluable for response. The first response evaluation is after the first 3 months of zanubrutinib. And then there were 0 response evaluations thereafter. So the median follow-up is [about] 12 months. The ORR is 97% already, which is really quite remarkable, especially given the high-risk patient population, but perhaps not too surprising, because we're combining 2 of our best agents that we have in CLL. So I think that's really quite exciting. Thus far, there's only been 1 progression event, which was a localized progression without disease in other compartments. So that is also relatively good.

The CR rate is 14%, but that's still a moving target because patients need to be evaluated by bone marrow biopsy when they get a CR. And so there are other patients who potentially qualify who haven't been evaluated by bone marrow biopsy yet.