Zanubrutinib prolongs progression-free survival (PFS), when compared with ibrutinib, in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), according to results of the phase 3 ALPINE study.

This is the first study to demonstrate PFS superiority in a head-to-head comparison of BTK inhibitors in patients with relapsed/refractory CLL/SLL, said Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston.

Dr Brown presented results from ALPINE at the 2022 ASH Annual Meeting.

Continue Reading

The trial ( Identifier: NCT03734016) enrolled 652 patients with relapsed/refractory CLL/SLL. They were randomly assigned to receive zanubrutinib (n=327) or ibrutinib (n=325). Demographics and disease characteristics were well balanced between the arms. 

At a median follow-up of 29.6 months, zanubrutinib was associated with a 35% reduction in the risk of progression or death (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P =.0024).  The 2-year PFS rate was 79.5% with zanubrutinib and 67.3% with ibrutinib.

PFS results favored zanubrutinib across subgroups, including among patients with del(17p)/TP53 mutation. The 2-year PFS rate in this subgroup was 77.6% with zanubrutinib and 55.7% with ibrutinib (HR, 0.52; 95% CI, 0.30-0.88; P =.0134).

The objective response rate was higher with zanubrutinib than with ibrutinib — 86.2% and 75.7%, respectively (P =.0007). 

Numerically, there were fewer deaths with zanubrutinib than with ibrutinib, but this did not reach statistical significance (HR, 0.76; 95% CI, 0.51-1.11).

Grade 3-5 adverse events (AEs) occurred in 67.3% of patients in the zanubrutinib arm and 70.4% of those in the ibrutinib arm. Grade 5 AEs occurred in 10.2% and 11.1%, respectively. 

The most common AEs in both arms were neutropenia, COVID-19-related events, and hypertension. The rate of cardiac AEs was 21.3% in the zanubrutinib arm and 29.6% in the ibrutinib arm. The rate of serious cardiac AEs was 1.9% and 7.7%, respectively. The rate of atrial fibrillation/flutter was 5.2% and 13.3%, respectively (P =.0004).

Disclosures: This research was supported by BeiGene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib demonstrates superior progression-free survival (PFS) compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): Results from final analysis of ALPINE randomized phase 3 study. Presented at ASH 2022. December 10-13, 2022. Abstract LBA-6.