Zanubrutinib in the treatment of patients with del(17p) and/or TP53 CLL/SLL: analysis across clinical studies.
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All Authors
Tam, CS.
Anderson, MA.
Simkovic, M.
Ghia, P.
Flinn, IW.
Laribi, K.
Opat, SS.
Cull, G.
Munir, T.
Osterborg, A.
LTHT Author
Munir, Talha
LTHT Department
Oncology
Haematology
Haematology
Non Medic
Publication Date
2025
Item Type
Journal Article
Language
Subject
Subject Headings
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; n=169, relapsed/refractory), data from SEQUOIA (phase 3; treatment-naive; zanubrutinib; NCT03336333), ALPINE (phase 3; relapsed/refractory; zanubrutinib versus ibrutinib; NCT03734016) and AU-003 (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 zanubrutinib-treated patients and 38.5% among ibrutinib-treated patients, and OS rates were 73.6% and 72.5%, respectively. In AU-003 (n=24; median follow-up, 69.6 months), 10/24 patients experienced progressive disease. Rate of response with zanubrutinib in SEQUOIA was 96.9% (95% CI: 95.2-98.8), in ALPINE was 89.3% (95% CI: 80.1-95.3) with zanubrutinib versus 76.0% (95% CI, 64.7-85.1%) with ibrutinib. Responses deepened over time in both treatment-naive and relapsed/refractory populations. The most frequent non-hematologic treatment-emergent adverse events occurring in >20% zanubrutinib-treated patients 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 relapsed/refractory settings.
Journal
Blood Advances