Zanubrutinib for the treatment of patients with del(17p) and/or TP53 CLL/SLL: analysis across clinical studies
Year: 2025
Type: article
Abstract: 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.
Source: Blood Advances
Authors: Constantine S. Tam, Mary Ann Anderson, Martin Šimkovič, Paolo Ghia, Ian W. Flinn, Kamel Laribi, Stephen Opat, Gavin Cull, Talha Munir, Anders Österborg, Alessandra Tedeschi, Megan Wang, Andy Szeto, Heather Allewelt, Tommi Salmi, Jessica Li, Linlin Xu, Kenneth Wu, Remus Vezan, Mazyar Shadman, Jennifer R. Brown
Institutions: The Alfred Hospital, Monash University, The Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research, Peter MacCallum Cancer Centre, Charles University, University Hospital Hradec Králové, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Tennessee Oncology, Centre Hospitalier du Mans, Monash Health, Sir Charles Gairdner Hospital, Leeds Teaching Hospitals NHS Trust, Karolinska University Hospital, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, BeOne Medicines (Switzerland), University of Washington, Fred Hutch Cancer Center, Dana-Farber Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4413316653