After a median follow-up of 42.5 months, zanubrutinib resulted in a sustained progression-free survival (PFS) benefit compared with ibrutinib, with responses deepening over time, in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
The study was led by Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute, and published in Blood.
Previous results of the ALPINE study showed improvement in outcomes for zanubrutinib-treated patients compared with ibrutinib. This latest study provided the final comparative analysis with extended follow-up. A total of 652 patients have received treatment: 327 with zanubrutinib 160 mg twice daily and 325 with ibrutinib 420 mg once daily. The overall median follow-up is 43.4 months with zanubrutinib and 41.6 months with ibrutinib.
The PFS benefit of zanubrutinib versus ibrutinib was sustained (HR, 0.68; 95% CI, 0.54-0.84), including in patients with del(17p)/TP53 mutation (HR, 0.51; 95% CI, 0.33-0.78). The 36-month PFS was 65.4% with zanubrutinib and 54.4% with ibrutinib.
The overall response rate remained higher in zanubrutinib-treated patients compared with ibrutinib-treated patients (85.6% vs 75.4%). Responses also deepened over time, with complete response or complete response with incomplete bone marrow recovery rates of 11.6% with zanubrutinib and 7.7% with ibrutinib.
Overall survival has not been reached in either treatment cohort.
Fewer patients in the zanubrutinib cohort discontinued treatment due to adverse events (21.4% vs 28.3%) or disease progression (18.0% vs 22.5%).
The most common nonhematologic adverse events in the zanubrutinib and ibrutinib cohorts were COVID-19-related infection (46.0% vs 33.3%), diarrhea (18.8% vs 25.6%), upper respiratory tract infection (29.3% vs 19.8%), and hypertension (27.2% vs 25.3%).
Cardiac events occurred in 25.9% of zanubrutinib patients and 35.5% of ibrutinib patients; no cardiac deaths were reported with zanubrutinib, though six cardiac deaths occurred with ibrutinib.
The study is limited by its open-label design and somewhat limited follow-up.
“The ALPINE study is, to our knowledge, the only head-to-head study of covalent or noncovalent [Bruton tyrosine kinase inhibitors] to show superior efficacy,” the authors concluded. “Now, with median study follow-up of 42.5 months, zanubrutinib has been shown to offer a sustained PFS benefit [versus] ibrutinib, with a 32% reduction in risk of progression or death.”
The study was funded by BeiGene.
Reference
Brown JR, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024;144(26):2706-2717. doi:10.1182/blood.2024024667
