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, 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 (Hillmen, P, EHA 2021, LB1900)
• 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
• Conclusions: efficacy
  • In the overall study population, a significantly higher ORR (PR + CR) was seen in the zanubrutinib arm:
    • zanubrutinib: 78.3%; ibrutinib: 62.5%
  • In patients with del(17p), a higher ORR was also seen for zanubrutinib:
    • zanubrutinib: 83.3%; ibrutinib: 53.8%
  • 12-month landmark PFS rate: zanubrutinib: 94.9%; ibrutinib: 84.0% (HR 0.4; 95% CI 0.23-0.69)
• Conclusions: safety
  • 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.