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

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.

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Publication Details

Journal
Blood Advances
Published
2025-08-19
DOI
https://doi.org/10.1182/bloodadvances.2025015986
Citations
1
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
1.63

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article

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

Ian W. Flinn, Gavin Cull, Alessandra Tedeschi, Kamel Laribi et al.
1 citations
Blood Advances
Chronic Lymphocytic Leukemia Research
1.63
article

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

Ian W. Flinn, Gavin Cull, Alessandra Tedeschi, Kamel Laribi, Jennifer R. Brown, Talha Munir, Tommi Salmi, Remus Vezan, Megan Wang, Constantine Si Lun Tam, Kenneth K. Wu, Andy H. Szeto, Mazyar Shadman, Heather Allewelt, Anders Österborg, Martin Šimkovič, Paolo Ghia, Stephen Opat, Mary Ann Anderson, Jessica Li, Linlin Xu
article en
1 citations

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.

Blood AdvancesVol. 10(3)
Karolinska University Hospital (SE), Vita-Salute San Raffaele University (IT), National University of Misiones (AR), Walter and Eliza Hall Institute of Medical Research (AU), University of Washington (US), Charles University (CZ), Leeds Teaching Hospitals NHS Trust (GB), Peter MacCallum Cancer Centre (AU), The Alfred Hospital (AU), Sir Charles Gairdner Hospital (AU), Fred Hutch Cancer Center (US), Monash Alfred Psychiatry Research centre (AU), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), NBE Therapeutics (Switzerland) (CH), Dana-Farber Cancer Institute (US), Monash Health (AU), Centre Hospitalier du Mans (FR), IRCCS Ospedale San Raffaele (IT), Tennessee Oncology (US), University Hospital Hradec Králové (CZ), Dionea (Switzerland) (CH), Universidad San Carlos (PY), Monash University (AU)
Eli Lilly and Company, AstraZeneca, Sanofi, Gilead Sciences, Celgene, St. Jude Children's Research Hospital, Swedish Orphan Biovitrum, National Health and Medical Research Council, Cilag
Openalex Percentile: Top 14%
Chronic Lymphocytic Leukemia Research
1.63
DOIOpen Access PDFOpenAlex
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