New Protocol: Zanubrutinib with Venetoclax for Untreated CLL

Phase 2, nonrandomized cohort within SEQUOIA trial (SEQUOIA Arm D)

Treatment-naïve CLL/SLL patients with or without TP53-aberrant disease

Zanubrutinib from cycle 1 + venetoclax ramp-up from cycle 4 to 28, followed by continuous zanubrutinib until progression or uMRD-based stop

ORR: 97% (TP53-aberrant: 99%, non-aberrant: 96%)

CR/CRi: 47% vs. 49% (TP53-aberrant vs. non-aberrant)

PB-uMRD at any time: 59% vs. 60%

24-mo PFS: 94% vs. 89% (TP53-aberrant vs. non-aberrant) (95% CI: [85%-98%] vs. [76%-95%])

36-mo PFS (TP53-aberrant): 88% [75%-94%]

Grade ≥3 AEs: Neutropenia (17%), hypertension (10%), diarrhea (6%)

Any-grade AEs: COVID-19 (54%), diarrhea (41%), nausea (30%)

Serious AEs: 31%

AEs leading to death: 4%

Shadman M,Munir T,Ma S Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/TP53 Mutation: SEQUOIA Arm D Results

Reviewed by Ulas D. Bayraktar, MD on Jun 2, 2025