SEQUOIA Trial: Zanubrutinib, Venetoclax Combination Effective in CLL

Zanubrutinib plus venetoclax exhibited promising efficacy and tolerability in patients with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma with del(17p) or TP53 mutations, according to a study presented at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.

The study, led by Shuo Ma, MD, PhD, of the Lurie Cancer Center, presented preliminary results from a nonrandomized cohort of patients from the phase III SEQUOIA trial. Sixty-six patients received zanubrutinib lead-in at 160 mg twice a day for three cycles, zanubrutinib and venetoclax ramp-up to 400 mg once a day for 24 cycles, then zanubrutinib monotherapy until progressive disease, unacceptable toxicity, or achievement of both complete response (CR) and undetectable measurable residual disease (MRD).

At a median follow-up of 28.6 months, the overall response rate was 100%, and the CR plus CR with incomplete hematopoietic recovery rate was 45%. Forty-eight percent of patients achieved undetectable MRD. While the median progression-free survival (PFS) was not reached, the 36-month PFS was estimated to be 92% (95% CI, 81%-97%).

Almost all (97%) patients experienced grade 1 or higher treatment-emergent adverse events (TEAEs). Forty-four percent experienced grade 3 or higher nonhematologic TEAEs, most commonly diarrhea (8%) and hypertension (8%). The most common nonhematologic TEAEs of any grade were COVID-19 (55%), diarrhea (41%), contusion (29%), and nausea (29%). The most common hematologic TEAE was neutropenia (21%), with grade 3 or higher neutropenia occurring in 17% of patients.

“The safety profile of [zanubrutinib plus venetoclax] was consistent with results of prior [zanubrutinib] studies, and no new safety signals were identified,” the researchers concluded.

Reference

Ma S, Munir T, Lasica M, et al. Combination of zanubrutinib + venetoclax for treatment-naive (tn) CLL/SLL with del(17p) and/or TP53: preliminary results from SEQUOIA arm D. Abstract #S160. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.