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Jennifer R. Brown, MD, PhD


ASH 2022: Final Analysis of Head-to-Head Comparison of BTK Inhibitors in Resistant CLL

By: Julia Fiederlein Cipriano
Posted: Wednesday, December 14, 2022

Based on a predefined response analysis of the phase III ALPINE trial, zanubrutinib demonstrated a superior overall response rate compared with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. The final progression-free survival analysis, which was presented by Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute, Boston, and colleagues during the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract LBA-6), continued to support zanubrutinib as the more efficacious Bruton’s tyrosine kinase (BTK) inhibitor in this setting.

Patients who received at least one prior therapy were randomly assigned in a 1:1 ratio to receive zanubrutinib (n = 327) or ibrutinib (n = 325). In the intention-to-treat population, independent review committee–assessed progression-free survival appeared to be superior with zanubrutinib compared with ibrutinib; investigator-assessed statistical values were found to be identical. The median duration of independent review committee–assessed progression-free survival was 35 months with ibrutinib and not reached with zanubrutinib.

Patients with del(17p)/TP53 mutations experienced longer durations of independent review committee–assessed progression-free survival with zanubrutinib than with ibrutinib. Progression-free survival seemed to consistently favor zanubrutinib across other major predefined subgroups. The independent review committee–assessed overall response (86.2% vs. 75.7%) and partial response with lymphocytosis or better (91.7% vs. 83.1%) rates were higher with zanubrutinib than with ibrutinib.

As for toxicity, patients treated with zanubrutinib experienced lower rates of adverse events of grade 3 or higher (67.3% vs. 70.4%), serious adverse events (42.0% vs. 50.0%), dose interruptions (50.0% vs. 56.8%), and dose reductions (12.3% vs. 17.0%) than those who received ibrutinib. The rates of atrial fibrillation/flutter were 5.2% and 13.3% with zanubrutinib and ibrutinib, respectively; the rates of other adverse events of special interest did not seem to differ between the arms. There were no grade 5 adverse events because of cardiac disorders with zanubrutinib; however, they were reported in 1.9% of patients treated with ibrutinib.

Disclosure: For full disclosures of the study authors, visit

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