TY - JOUR
T1 - Zanubrutinib Versus Bendamustine and Rituximab in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
T2 - Median 5-Year Follow-Up of SEQUOIA
AU - Shadman, Mazyar
AU - Munir, Talha
AU - Robak, Tadeusz
AU - Brown, Jennifer R.
AU - Kahl, Brad S.
AU - Ghia, Paolo
AU - Giannopoulos, Krzysztof
AU - Šimkovič, Martin
AU - Österborg, Anders
AU - Laurenti, Luca
AU - Walker, Patricia A.
AU - Opat, Stephen S.
AU - Ciepluch, Hanna
AU - Greil, Richard
AU - Hanna, Merit
AU - Tani, Monica
AU - Trněný, Marek
AU - Brander, Danielle
AU - Flinn, Ian W.
AU - Grosicki, Sebastian
AU - Verner, Emma
AU - Tedeschi, Alessandra
AU - De Guibert, Sophie
AU - Tumyan, Gayane
AU - Laribi, Kamel
AU - García-Marco, José A.
AU - Li, Jian Yong
AU - Tian, Tian
AU - Liu, Yu
AU - Korolkiewicz, Roman
AU - Szeto, Andy
AU - Tam, Constantine S.
AU - Jurczak, Wojciech
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2025/3/1
Y1 - 2025/3/1
N2 - Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-Treated patients; median PFS was 44.1 months in BR-Treated patients (hazard ratio [HR], 0.29; one-sided P =.0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P =.0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P <.0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib-and BR-Treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.
AB - Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-Treated patients; median PFS was 44.1 months in BR-Treated patients (hazard ratio [HR], 0.29; one-sided P =.0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P =.0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P <.0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib-and BR-Treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.
UR - https://www.scopus.com/pages/publications/85219510700
U2 - 10.1200/JCO-24-02265
DO - 10.1200/JCO-24-02265
M3 - Article
C2 - 39647999
AN - SCOPUS:85219510700
SN - 0732-183X
VL - 43
SP - 780
EP - 787
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -