Zanubrutinib for the treatment of patients with del(17p) and/or TP53 CLL/SLL: analysis across clinical studies

Tam, CS; Anderson, MA; Šimkovič, M; Ghia, P; Flinn, IW; Laribi, K; Opat, S; Cull, G; Munir, T; &#214;sterborg, A; Tedeschi, A; Wang, M; Szeto, A; Allewelt, H; Salmi, T; Li, J; Xu, L; Wu, K; Vezan, R; Shadman, M; Brown, JR

Author(s): Tam, CS; Anderson, MA; Šimkovič, M; Ghia, P; Flinn, IW; Laribi, K; Opat, S; Cull, G; Munir, T; Österborg, A; Tedeschi, A; Wang, M; Szeto, A; Allewelt, H; Salmi, T; Li, J; Xu, L; Wu, K; Vezan, R; Shadman, M; Brown, JR;
Details: Publication Year 2026-02-10,Volume 10,Issue #3,Page 694-706
Journal Title: Blood Advances
Publication Type: Research article
Abstract: Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who harbor del(17p) and/or tumor protein p53 (TP53) mutations represent a high-risk population with a historically poor prognosis. To assess zanubrutinib efficacy and safety outcomes in patients with CLL/SLL with del(17p) and/or TP53 mutations (N = 301; n = 132, treatment-naive [TN]; n = 169, relapsed/refractory [R/R]), data from SEQUOIA (phase 3; TN; zanubrutinib; NCT03336333), ALPINE (phase 3; R/R; zanubrutinib vs ibrutinib; NCT03734016), and AU-003 (NCT02343120) (phase 1/2; zanubrutinib) were evaluated. In SEQUOIA (n = 127; median follow-up, 64.8 months), median progression-free survival (PFS) and overall survival (OS) were not reached; estimated 60-month PFS and OS were 70.7% and 82.3%, respectively. In ALPINE (n = 75, each treatment arm; median follow-up, 39.0 months), 36-month PFS rates were 59.2% among patients treated with zanubrutinib and 38.5% among those treated with ibrutinib, and OS rates were 73.6% and 72.5%, respectively. In AU-003 (n = 24; median follow-up, 69.6 months), 10 of 24 patients experienced progressive disease. Rate of response with zanubrutinib in SEQUOIA was 96.9% (95% confidence interval [CI], 95.2-98.8), and in ALPINE was 89.3% (95% CI, 80.1-95.3) with zanubrutinib vs 76.0% (95% CI, 64.7-85.1) with ibrutinib. Responses deepened over time in both TN and R/R populations. The most frequent nonhematologic treatment-emergent adverse events occurring in >20% of patients treated with zanubrutinib with del(17p) and/or TP53 mutations in SEQUOIA and ALPINE were COVID-19, upper respiratory tract infection, arthralgia, diarrhea, and contusion. In conclusion, zanubrutinib demonstrated strong efficacy in high-risk del(17p) and/or TP53 CLL/SLL, with a tolerable safety profile, further supporting use of zanubrutinib in both frontline and R/R settings.
Publisher: Elsevier
Keywords: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Adenine/analogs & derivatives/analogs & derivatives; *Antineoplastic Agents/therapeutic use/adverse effects; Chromosome Deletion; Chromosomes, Human, Pair 17/genetics; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/genetics/mortality; Mutation; *Piperidines/therapeutic use/adverse effects; Protein Kinase Inhibitors/therapeutic use/adverse effects; *Pyrazoles/therapeutic use/adverse effects/administration & dosage; *Pyrimidines/therapeutic use/adverse effects/administration & dosage; Treatment Outcome; *Tumor Suppressor Protein p53/genetics; Clinical Trials as Topic
Department(s): Haematology
Publisher's Version: https://doi.org/10.1182/bloodadvances.2025015986
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2025015986
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-02-03 06:11:43

Last Modified: 2026-02-03 06:11:50