Inhibition of B-cell receptor signalling via Bruton tyrosine kinase (BTK) has been a breakthrough for the treatment of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL).
Zanubrutinib is a next-generation BTK inhibitor that is designed for potent and sustained inhibition of BTK while minimising the off-target effects of first-generation inhibitors such as ibrutinib.
The activity and tolerability of zanubrutinib have been demonstrated in patients with CLL/SLL in early phase clinical trials.
The ALPINE study solidifies the findings of these pivotal trials by a head-to-head comparison of the safety and efficacy of zanubrutinib and ibrutinib in 415 patients with relapsed/refractory CLL/SLL.
Our interim analysis at 12 months after enrolment revealed that the overall response rate in zanubrutinib-treated patients was significantly higher than those treated with ibrutinib (78.3% vs 62.5%).
Similarly, overall progression-free survival and overall survival rates were higher in the zanubrutinib group and zanubrutinib outperformed ibrutinib in several safety outcomes including rate of atrial fibrillation/flutter, major bleeding, adverse events leading to discontinuation, and grade ≥3 infection.
However, zanubrutinib treatment increased the rate of neutropenia compared with ibrutinib (28.4% vs 21.7%).
In summary, zanubrutinib showed more selective inhibition of BTK resulting in improved efficacy and safety compared with ibrutinib.
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