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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) chronic lymphocytic leukemia (CLL). Investigators from multiple CLL centers in Europe, Australia, and North America were involved in this research.
CLL treatment significantly changed for the better with the introduction of the first irreversible Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, in 2014 in the USA, which today has become a 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 reduce side effects, and that its better binding to the BTK receptor might increase its efficacy. In other words, it was designed to better inhibit BTK and as little else as possible,
ALPINE is a global, randomized, phase 3 study comparing zanubrutinib versus ibrutinib in patients with relapsed/refractory (R/R) CLL.
The EHA 2021 presentation shares the results of a pre-planned analysis approximately
12 months once 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, overall response rate or 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 or PFS (94.9% vs 84.0%), and overall survival or OS rates (97.0% vs 92.7%), also favored 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.
- Rate of low neutrophil counts or 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 really will 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. And that question will only be answered with more time and data. These early results give CLL patients reasons to be hopeful.
Here is the link to the late breaking EHA 2021 abstract.
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Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.