Jennifer R. Brown, MD, PhD, discusses data from the following presentation:

First interim analysis of the ALPINE study: a phase III randomized trial of zanubrutinib vs. ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (

The objective of this study is to report the interim analysis, including efficacy and safety outcomes from the ALPINE trial (NCT03734016).

Phase III trial compared zanubrutinib (160 mg twice daily) with ibrutinib (420 mg once daily)

Patients were randomized 1:1 (zanubrutinib, n=207; ibrutinib, n=208)

Primary end point: overall response rate (ORR) (partial response (PR) + complete response (CR)) noninferiority and superiority as assessed by investigator

Secondary end points: atrial fibrillation, duration of response, progression-free survival (PFS), overall survival, time to treatment failure, PR with lymphocytosis (PR-L) or higher, patient-reported outcomes, safety

Preplanned interim analysis: data cutoff approximately 12 months after the randomization of 415 patients

Baseline patient and disease characteristics were similar between the arms

In the overall study population, a significantly higher ORR (PR + CR) was seen in the zanubrutinib arm:

In patients with del(17p), a higher ORR was also seen for zanubrutinib:

12-month landmark PFS rate: zanubrutinib: 94.9%; ibrutinib: 84.0% (HR 0.4; 95% CI 0.23-0.69)

Similar safety profiles were seen with both treatments; however, any grade atrial fibrillation was demonstrated in 2.5% of patients in the zanubrutinib arm and 10.1% of patients in the ibrutinib arm.

In this interim analysis, zanubrutinib was shown to have superior response rate, improved PFS, and a lower rate of atrial fibrillation then ibrutinib.

These data suggest that zanubrutinib’s more complete and sustained BTK occupancy may result in better efficacy and safety outcomes than those seen with the first-generation BTK inhibitor, ibrutinib.

Videos

Jennifer R. Brown, MD, PhD presents an interim analysis from the ALPINE study of zanubrutinib vs. ibrutinib in patients with R/R CLL/SLL presented at the 2021 European Hematology Association virtual congress.

Rapid Readouts: First interim analysis of the ALPINE study: a phase III randomized trial of zanubrutinib vs. ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

Jennifer R. Brown, MD, PhD, Dana Farber Cancer Institute

Articles

Rapid Readouts: First interim analysis of the ALPINE study: a phase III randomized trial of zanubrutinib vs. ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma