TY - JOUR
T1 - Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
AU - Brown, Jennifer R.
AU - Eichhorst, Barbara
AU - Hillmen, Peter
AU - Jurczak, Wojciech
AU - Kaźmierczak, Maciej
AU - Lamanna, Nicole
AU - O'brien, Susan M.
AU - Tam, Constantine S.
AU - Qiu, Lugui
AU - Zhou, Keshu
AU - Simkovic, Martin
AU - Mayer, Jiri
AU - Gillespie-Twardy, Amanda
AU - Ferrajoli, Alessandra
AU - Ganly, Peter S.
AU - Weinkove, Robert
AU - Grosicki, Sebastian
AU - Mital, Andrzej
AU - Robak, Tadeusz
AU - Osterborg, Anders
AU - Yimer, Habte A.
AU - Salmi, Tommi
AU - Wang, Megan Der Yu
AU - Fu, Lina
AU - Li, Jessica
AU - Wu, Kenneth
AU - Cohen, Aileen
AU - Shadman, Mazyar
N1 - Publisher Copyright:
© 2022 Massachusetts Medical Society.
PY - 2023
Y1 - 2023
N2 - Background: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available. Methods: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05. Results: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P=0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death. Conclusions: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events.
AB - Background: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available. Methods: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05. Results: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P=0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death. Conclusions: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events.
KW - Hematology/Oncology
KW - Leukemia/Lymphoma
KW - Treatments in Oncology
UR - http://www.scopus.com/inward/record.url?scp=85144489593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144489593&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2211582
DO - 10.1056/NEJMoa2211582
M3 - Article
C2 - 36511784
AN - SCOPUS:85144489593
SN - 0028-4793
VL - 388
SP - 319
EP - 332
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 4
ER -