Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic
Lymphocytic Leukemia

J 2023

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia

BROWN, Jennifer; Barbara EICHHORST; Peter HILLMEN; Wojciech JURCZAK; Maciej KAZMIERCZAK et. al.

Basic information

Original name

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia

Authors

BROWN, Jennifer (guarantor); Barbara EICHHORST; Peter HILLMEN; Wojciech JURCZAK; Maciej KAZMIERCZAK; Nicole LAMANNA; Susan BRIEN; Constantine TAM; Lugui QIU; Keshu ZHOU; Martin SIMKOVIC; Jiří MAYER (203 Czech Republic, belonging to the institution); Amanda GILLESPIE-TWARDY; Alessandra FERRAJOLI; Peter GANLY; Robert WEINKOVE; Sebastian GROSICKI; Andrzej MITAL; Tadeusz ROBAK; Anders OSTERBORG; Habte YIMER; Tommi SALMI; Megan-Der-Yu WANG; Lina FU; Jessica LI; Kenneth WU; Aileen COHEN and Mazyar SHADMAN

Edition

New England Journal of Medicine, Waltham, Massachussetts Medical Society, 2023, 0028-4793

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 96.300

RIV identification code

RIV/00216224:14110/23:00130133

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1056/NEJMoa2211582

UT WoS

000898578200001

EID Scopus

2-s2.0-85144489593

Keywords in English

Zanubrutinib; Ibrutinib; Chronic Lymphocytic Leukemia

Abstract

V originále

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. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, .)

Files attached

Zanubrutinib_or_Ibrutinib_in_Relapsed_or_Refractory_Chronic_Lymphocytic_Leukemia.pdf

Request the author's version of the file

Cite

BROWN, Jennifer; Barbara EICHHORST; Peter HILLMEN; Wojciech JURCZAK; Maciej KAZMIERCZAK; Nicole LAMANNA; Susan BRIEN; Constantine TAM; Lugui QIU; Keshu ZHOU; Martin SIMKOVIC; Jiří MAYER; Amanda GILLESPIE-TWARDY; Alessandra FERRAJOLI; Peter GANLY; Robert WEINKOVE; Sebastian GROSICKI; Andrzej MITAL; Tadeusz ROBAK; Anders OSTERBORG; Habte YIMER; Tommi SALMI; Megan-Der-Yu WANG; Lina FU; Jessica LI; Kenneth WU; Aileen COHEN and Mazyar SHADMAN. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. New England Journal of Medicine. Waltham: Massachussetts Medical Society, 2023, vol. 388, No 4, p. 319-332. ISSN 0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2211582.

@article{2243400,
   author = {Brown, Jennifer and Eichhorst, Barbara and Hillmen, Peter and Jurczak, Wojciech and Kazmierczak, Maciej and Lamanna, Nicole and Brien, Susan and Tam, Constantine and Qiu, Lugui and Zhou, Keshu and Simkovic, Martin and Mayer, Jiří and GillespieandTwardy, Amanda and Ferrajoli, Alessandra and Ganly, Peter and Weinkove, Robert and Grosicki, Sebastian and Mital, Andrzej and Robak, Tadeusz and Osterborg, Anders and Yimer, Habte and Salmi, Tommi and Wang, MeganandDerandYu and Fu, Lina and Li, Jessica and Wu, Kenneth and Cohen, Aileen and Shadman, Mazyar},
   article_location = {Waltham},
   article_number = {4},
   doi = {http://dx.doi.org/10.1056/NEJMoa2211582},
   keywords = {Zanubrutinib; Ibrutinib; Chronic Lymphocytic Leukemia},
   language = {eng},
   issn = {0028-4793},
   journal = {New England Journal of Medicine},
   title = {Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia},
   url = {https://www.nejm.org/doi/full/10.1056/NEJMoa2211582},
   volume = {388},
   year = {2023}
}

TY  - JOUR
ID  - 2243400
AU  - Brown, Jennifer - Eichhorst, Barbara - Hillmen, Peter - Jurczak, Wojciech - Kazmierczak, Maciej - Lamanna, Nicole - Brien, Susan - Tam, Constantine - Qiu, Lugui - Zhou, Keshu - Simkovic, Martin - Mayer, Jiří - Gillespie-Twardy, Amanda - Ferrajoli, Alessandra - Ganly, Peter - Weinkove, Robert - Grosicki, Sebastian - Mital, Andrzej - Robak, Tadeusz - Osterborg, Anders - Yimer, Habte - Salmi, Tommi - Wang, Megan-Der-Yu - Fu, Lina - Li, Jessica - Wu, Kenneth - Cohen, Aileen - Shadman, Mazyar
PY  - 2023
TI  - Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
JF  - New England Journal of Medicine
VL  - 388
IS  - 4
SP  - 319-332
EP  - 319-332
PB  - Massachussetts Medical Society
SN  - 00284793
KW  - Zanubrutinib
KW  - Ibrutinib
KW  - Chronic Lymphocytic Leukemia
UR  - https://www.nejm.org/doi/full/10.1056/NEJMoa2211582
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. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, .)
ER  -

BROWN, Jennifer; Barbara EICHHORST; Peter HILLMEN; Wojciech JURCZAK; Maciej KAZMIERCZAK; Nicole LAMANNA; Susan BRIEN; Constantine TAM; Lugui QIU; Keshu ZHOU; Martin SIMKOVIC; Jiří MAYER; Amanda GILLESPIE-TWARDY; Alessandra FERRAJOLI; Peter GANLY; Robert WEINKOVE; Sebastian GROSICKI; Andrzej MITAL; Tadeusz ROBAK; Anders OSTERBORG; Habte YIMER; Tommi SALMI; Megan-Der-Yu WANG; Lina FU; Jessica LI; Kenneth WU; Aileen COHEN and Mazyar SHADMAN. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. \textit{New England Journal of Medicine}. Waltham: Massachussetts Medical Society, 2023, vol.~388, No~4, p.~319-332. ISSN~0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2211582.

Přehled o publikaci