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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F23%3A00076693" target="_blank" >RIV/65269705:_____/23:00076693 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/23:00130697 RIV/00216208:11150/23:10465236 RIV/00179906:_____/23:10465236

Result on the web

<a href="https://ascopubs.org/doi/pdf/10.1200/JCO.22.00510?role=tab" target="_blank" >https://ascopubs.org/doi/pdf/10.1200/JCO.22.00510?role=tab</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1200/JCO.22.00510" target="_blank" >10.1200/JCO.22.00510</a>

Result language

angličtina

Original language name

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

Original language description

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: NCT03734016) 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 &lt; .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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Clinical Oncology

ISSN

0732-183X

e-ISSN

1527-7755

Volume of the periodical

41

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

1035-"+"

UT code for WoS article

000946950600015

EID of the result in the Scopus database

2-s2.0-85147720922