Zanubrutinib and Venetoclax for Patients With Treatment-Naive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/TP53 Mutation: SEQUOIA Arm D Results.

Shadman, M.; Munir, T.; Ma, S.; Lasica, M.; Tani, M.; Robak, T.; Flinn, IW.; Brown, JR.; Ghia, P.; Ferrant, E.; Tam, CS.; Janowski, W.; Jurczak, W.; Xu, L.; Tian, T.; Lefebure, M.; Agresti, S.; Hirata, J.; Tedeschi, A.

Zanubrutinib and Venetoclax for Patients With Treatment-Naive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/TP53 Mutation: SEQUOIA Arm D Results.

All Authors

Shadman, M.

Munir, T.

Ma, S.

Lasica, M.

Tani, M.

Robak, T.

Flinn, IW.

Brown, JR.

Ghia, P.

Ferrant, E.

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LTHT Author

Munir, Talha

LTHT Department

Oncology
Haematology

Publication Date

2025

Item Type

Clinical Trial
Journal Article
Multicenter Study

Abstract

PURPOSE: Several chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and/or TP53 mutation (TP53mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-naive (TN) patients with CLL/small lymphocytic lymphoma (SLL), in a large population of patients with TP53-aberrant disease. PATIENTS AND METHODS: Arm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria. RESULTS: Between November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with TP53-aberrant disease, 47 (41%) without TP53-aberrant disease, and 1 with missing TP53 results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade >=3 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%). CONCLUSION: Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of TP53-aberrant disease.