Among patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), zanubrutinib appears to yield superior clinical outcomes to ibrutinib, according to research presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO).
Bruton tyrosine kinase inhibitors have transformed the CLL/SLL treatment landscape. Improvements were noted in particular with the introduction of ibrutinib; zanubrutinib, however, is a next-generation inhibitor of Bruton tyrosine kinase that preclinical studies have suggested is both more selective and less likely to lead to toxicity.
Researchers designed the randomized phase 3 ALPINE trial (ClinicalTrials.gov Identifier: NCT03734016) to compare the safety and efficacy of zanubrutinib and ibrutinib among patients with relapsed/refractory CLL/SLL. At the 2022 SOHO meeting, the authors presented results of a preplanned interim analysis.
Overall, 415 patients were randomly assigned 1:1 to receive ibrutinib or zanubrutinib. Patients were stratified by age, refractory disease status, and the presence of 17p deletion or TP53 mutation. The interim analysis was conducted at approximately 1-year post enrollment for all patients.
In the zanubrutinib vs ibrutinib group, 62.3% vs 61.5% of patients were at least 65 years old, respectively, 68.6% vs 75% of patients were male sex, and 7.2% vs 10.1% of patients had received more than 3 prior therapy lines. TP53 mutations without 17p deletion were noted in 8.2% of patients in the zanubrutinib group vs 5.8% of patients in the ibrutinib group.
The median follow-up was 15 months. At this point, the overall response rate was 78.3% in the zanubrutinib group vs 62.5% in the ibrutinib group (2-sided P =.0006). Improved overall response rates were noted among patients with 11q deletion or 17p deletion.
Analysis suggested that 12-month progression-free survival (94.9% vs 84.0%) and 12-month overall survival (97.0% vs 92.7%) were improved in the zanubrutinib vs ibrutinib group, respectively.
Lower rates of major bleeding (2.9% vs 3.9%), toxicity leading to discontinuation (7.8% vs 13.0%), grade 3 or worse infection (12.7% vs 17.9%), and death (3.9% vs 5.8%) were noted in the zanubrutinib vs ibrutinib group, respectively, though neutropenia occurred more frequently (28.4% vs 21.7%).
Brown JR, Hillmen P, Eichhorst B, et al. First interim analysis of ALPINE study: results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL). Annual Meeting of the Society of Hematologic Oncology (SOHO); September 28-October 1, 2022. Abstract CLL-115.