Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic
Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim
Analysis of a Randomized Phase III Trial

J 2023

Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial

HILLMEN, Peter, Barbara EICHHORST, Jennifer R BROWN, Nicole LAMANNA, Susan M BRIEN et. al.

Basic information

Original name

Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial

Authors

HILLMEN, Peter (guarantor), Barbara EICHHORST, Jennifer R BROWN, Nicole LAMANNA, Susan M BRIEN, Constantine S TAM, Lugui QIU, Maciej KAZMIERCZAK, Keshu ZHOU, Martin SIMKOVIC, Jiří MAYER (203 Czech Republic, belonging to the institution), Amanda GILLESPIE-TWARDY, Mazyar SHADMAN, Alessandra FERRAJOLI, Peter S GANLY, Robert WEINKOVE, Sebastian GROSICKI, Andrzej MITAL, Tadeusz ROBAK, Anders OSTERBORG, Habte A YIMER, Tommi SALMI, Meng JI, Jessica YECIES, Adam IDOINE, Kenneth WU, Jane HUANG and Wojciech JURCZAK

Edition

Journal of clinical oncology, United States, LIPPINCOTT WILLIAMS & WILKINS, 2023, 0732-183X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 45.300 in 2022

RIV identification code

RIV/00216224:14110/23:00130697

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1200/JCO.22.00510

UT WoS

000946950600015

Keywords in English

Zanubrutinib; Ibrutinib; Relapsed/Refractory Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Abstract

V originále

PURPOSE Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities.PATIENTS AND METHODS ALPINE (ClinicalTrials.gov identifier: ) is a global, randomized, open-label phase III study of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The primary end point was investigator-assessed overall response rate (ORR). The preplanned interim analysis was scheduled approximately 12 months after the first 415 patients were enrolled.RESULTS Between November 1, 2018, and December 14, 2020, 652 patients were enrolled. We present the interim analysis of the first 415 enrolled patients randomly assigned to receive zanubrutinib (n = 207) or ibrutinib (n = 208). At 15 months of median follow-up, ORR (partial or complete response) was significantly higher with zanubrutinib (78.3%; 95% CI, 72.0 to 83.7) versus ibrutinib (62.5%; 95% CI, 55.5 to 69.1; two-sided P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%); 12-month progression-free survival in all patients was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69). Atrial fibrillation rate was significantly lower with zanubrutinib versus ibrutinib (2.5% v 10.1%; two-sided P = .001). Rates of cardiac events, major hemorrhages, and adverse events leading to treatment discontinuation/death were lower with zanubrutinib.CONCLUSION Zanubrutinib had a significantly higher ORR, lower atrial fibrillation rate, and improved progression-free survival and overall cardiac safety profile versus ibrutinib. These data support improved efficacy/safety outcomes with selective BTK inhibition.

Citovat

HILLMEN, Peter, Barbara EICHHORST, Jennifer R BROWN, Nicole LAMANNA, Susan M BRIEN, Constantine S TAM, Lugui QIU, Maciej KAZMIERCZAK, Keshu ZHOU, Martin SIMKOVIC, Jiří MAYER, Amanda GILLESPIE-TWARDY, Mazyar SHADMAN, Alessandra FERRAJOLI, Peter S GANLY, Robert WEINKOVE, Sebastian GROSICKI, Andrzej MITAL, Tadeusz ROBAK, Anders OSTERBORG, Habte A YIMER, Tommi SALMI, Meng JI, Jessica YECIES, Adam IDOINE, Kenneth WU, Jane HUANG and Wojciech JURCZAK. Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial. Journal of clinical oncology. United States: LIPPINCOTT WILLIAMS & WILKINS, 2023, vol. 41, No 5, p. "1035"-"+", 12 pp. ISSN 0732-183X. Available from: https://dx.doi.org/10.1200/JCO.22.00510.

@article{2279453,
   author = {Hillmen, Peter and Eichhorst, Barbara and Brown, Jennifer R and Lamanna, Nicole and Brien, Susan M and Tam, Constantine S and Qiu, Lugui and Kazmierczak, Maciej and Zhou, Keshu and Simkovic, Martin and Mayer, Jiří and GillespieandTwardy, Amanda and Shadman, Mazyar and Ferrajoli, Alessandra and Ganly, Peter S and Weinkove, Robert and Grosicki, Sebastian and Mital, Andrzej and Robak, Tadeusz and Osterborg, Anders and Yimer, Habte A and Salmi, Tommi and Ji, Meng and Yecies, Jessica and Idoine, Adam and Wu, Kenneth and Huang, Jane and Jurczak, Wojciech},
   article_location = {United States},
   article_number = {5},
   doi = {http://dx.doi.org/10.1200/JCO.22.00510},
   keywords = {Zanubrutinib; Ibrutinib; Relapsed/Refractory Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma},
   language = {eng},
   issn = {0732-183X},
   journal = {Journal of clinical oncology},
   title = {Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial},
   url = {https://ascopubs.org/doi/10.1200/JCO.22.00510},
   volume = {41},
   year = {2023}
}

TY  - JOUR
ID  - 2279453
AU  - Hillmen, Peter - Eichhorst, Barbara - Brown, Jennifer R - Lamanna, Nicole - Brien, Susan M - Tam, Constantine S - Qiu, Lugui - Kazmierczak, Maciej - Zhou, Keshu - Simkovic, Martin - Mayer, Jiří - Gillespie-Twardy, Amanda - Shadman, Mazyar - Ferrajoli, Alessandra - Ganly, Peter S - Weinkove, Robert - Grosicki, Sebastian - Mital, Andrzej - Robak, Tadeusz - Osterborg, Anders - Yimer, Habte A - Salmi, Tommi - Ji, Meng - Yecies, Jessica - Idoine, Adam - Wu, Kenneth - Huang, Jane - Jurczak, Wojciech
PY  - 2023
TI  - Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial
JF  - Journal of clinical oncology
VL  - 41
IS  - 5
SP  - "1035"-"+"
EP  - "1035"-"+"
PB  - LIPPINCOTT WILLIAMS & WILKINS
SN  - 0732183X
KW  - Zanubrutinib
KW  - Ibrutinib
KW  - Relapsed/Refractory Chronic Lymphocytic Leukemia
KW  - Small Lymphocytic Lymphoma
UR  - https://ascopubs.org/doi/10.1200/JCO.22.00510
N2  - PURPOSE Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities.PATIENTS AND METHODS ALPINE (ClinicalTrials.gov identifier: ) is a global, randomized, open-label phase III study of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The primary end point was investigator-assessed overall response rate (ORR). The preplanned interim analysis was scheduled approximately 12 months after the first 415 patients were enrolled.RESULTS Between November 1, 2018, and December 14, 2020, 652 patients were enrolled. We present the interim analysis of the first 415 enrolled patients randomly assigned to receive zanubrutinib (n = 207) or ibrutinib (n = 208). At 15 months of median follow-up, ORR (partial or complete response) was significantly higher with zanubrutinib (78.3%; 95% CI, 72.0 to 83.7) versus ibrutinib (62.5%; 95% CI, 55.5 to 69.1; two-sided P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%); 12-month progression-free survival in all patients was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69). Atrial fibrillation rate was significantly lower with zanubrutinib versus ibrutinib (2.5% v 10.1%; two-sided P = .001). Rates of cardiac events, major hemorrhages, and adverse events leading to treatment discontinuation/death were lower with zanubrutinib.CONCLUSION Zanubrutinib had a significantly higher ORR, lower atrial fibrillation rate, and improved progression-free survival and overall cardiac safety profile versus ibrutinib. These data support improved efficacy/safety outcomes with selective BTK inhibition.
ER  -

HILLMEN, Peter, Barbara EICHHORST, Jennifer R BROWN, Nicole LAMANNA, Susan M BRIEN, Constantine S TAM, Lugui QIU, Maciej KAZMIERCZAK, Keshu ZHOU, Martin SIMKOVIC, Jiří MAYER, Amanda GILLESPIE-TWARDY, Mazyar SHADMAN, Alessandra FERRAJOLI, Peter S GANLY, Robert WEINKOVE, Sebastian GROSICKI, Andrzej MITAL, Tadeusz ROBAK, Anders OSTERBORG, Habte A YIMER, Tommi SALMI, Meng JI, Jessica YECIES, Adam IDOINE, Kenneth WU, Jane HUANG and Wojciech JURCZAK. Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial. \textit{Journal of clinical oncology}. United States: LIPPINCOTT WILLIAMS \&{} WILKINS, 2023, vol.~41, No~5, p.~''1035''-''+'', 12 pp. ISSN~0732-183X. Available from: https://dx.doi.org/10.1200/JCO.22.00510.

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