Smart Patients Get Smart Care™

The World’s Leading Authority for Chronic Lymphocytic Leukemia Patients

EHA 2021 Top Pick #4: First Interim Analysis of the ALPINE Study: Results of a Phase 3 Randomized Study of Zanubrutinib Versus Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL / SLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

This was accepted as a late-breaking abstract at the 2021 European Hematology Association Virtual Congress (EHA) 2021, reflecting its importance to the best management of relapsed/refractory (R/R) CLL). Investigators from multiple CLL centers in Europe, Australia, and North America were involved in this research.


CLL treatment significantly changed for the better in 2014 with the introduction of the first irreversible Bruton’s tyrosine kinase inhibitor (BTKi), ibrutinib, which has become a current standard of care.

Zanubrutinib is also an irreversible BTK inhibitor similar to ibrutinib. It has been engineered to maximize BTK occupancy and minimize unwanted “off-target” inhibition of other enzymes, in the hopes that its increased specificity may both reduce side effects and increase its efficacy since it does a better job binding to the BTK receptor. In other words, it was designed to better inhibit BTK and do as little else as possible.

The ALPINE trial is a global, randomized, phase 3 study comparing zanubrutinib versus ibrutinib in patients with relapsed/refractory (R/R) CLL.

The EHA 2021 presentation shared the results of a pre-planned analysis approximately 12 months after the first 415 (out of 652) patients were enrolled.


  • Both arms of the trials were well balanced in terms of patient characteristics
  • At 15 months, the overall response rate (ORR) was higher with zanubrutinib versus ibrutinib (78.3% vs 62.5%). This was also true for those with poor markers such as del(11q) or del(17p).
  • 12-month progression-free survival (PFS) was 94.9% vs. 84.0%, and the overall survival (OS) rate was 97.0% vs. 92.7%, both favoring zanubrutinib
  • The rate of atrial fibrillation/flutter was significantly lower with zanubrutinib versus ibrutinib (2.5% vs 10.1%)
  • Rates of major bleeding (2.9% vs 3.9%), and adverse events leading to discontinuation (7.8% vs 13.0%) or death (3.9% vs 5.8%) were also slightly lower with zanubrutinib
  • The rate of low neutrophil counts (neutropenia) was higher with zanubrutinib (28.4% vs 21.7%)
  • Serious infections were less common with zanubrutinib (12.7% vs 17.9%)


These data suggest that zanubrutinib’s more selective BTK inhibition and better BTK occupancy may result in improved efficacy and safety outcomes. What we are seeing early on is encouraging. But what we will really be interested in finding out is if these early improved measures of efficacy mean that zanubrutinib can lead to a longer life for CLL patients. That question will only be answered with more time and data. These early results give CLL patients additional reasons to be hopeful.

Here is the link to the late-breaking EHA 2021 abstract.

Please enjoy the video:

Stay strong. We are all in this together.

Brian Koffman, MDCM (retired), MSEd
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society, Inc.