Dr Shadman on Zanubrutinib Plus Venetoclax in Treatment-Naive CLL/SLL

“This combination was extremely effective regardless of [the presence] of the TP53 aberrancy. We saw high overall response rates and complete response with incomplete hematopoietic recovery rates…across the 2 groups and in the entire population.”

Mazyar Shadman, MD, MPH, the medical director of Cellular Immunotherapy, an associate professor in the Clinical Research Division, a member of the Immunotherapy Integrated Research Center, and the Innovators Network Endowed Chair at Fred Hutchinson Cancer Center, discussed data from arm D of the phase 3 SEQUOIA trial (NCT03336333).

Arm D of SEQUOIA evaluated zanubrutinib (Brukinsa) in combination with venetoclax (Venclexta) for the first-line treatment of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Arm D of the study included patients with 17p deletions [del(17p)] and/or TP53-mutated disease and those without.

Data from SEQUOIA presented during the 2025 ASCO Annual Meeting showed that the overall response rates among patients with del(17p) and/or TP53-mutated disease (n = 66), those without del(17p) and TP53-mutated disease (n = 47), and the overall cohort (n = 114) were 98.5%, 95.7%, and 97.4%, respectively. The respective complete response with incomplete hematopoietic recovery rates were 47.0%, 48.9%, and 48.3%, Shadman said.

Another important finding from the study was the high rates of undetectable minimal residual disease (uMRD), which were observed across both groups and in the overall population, Shadman added. The uMRD rates in patients with del(17p) and/or TP53-mutated disease, those without del(17p) and TP53-mutated disease, and in the overall cohort were 59%, 60%, and 59%, respectively. These data are significant because the combination of zanubrutinib and venetoclax is an all-oral regimen that does not include an anti-CD20 antibody, he said.

Shadman noted that the uMRD rate was 43% in patients without del(17p) and TP53-mutated disease by cycle 16 which increased to 60% by cycle 28. In those with del(17p) and/or TP53-mutated disease, the respective rates at these time points were 21% and 49%. This increase in the higher-risk group underscores the importance of continuing therapy in patients with this disease profile, he said. These patients may eventually achieve uMRD but it may take longer if their disease harbors an abnormal p53 gene, Shadman concluded.