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Zanubrutinib vs. Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia

The greater specificity of zanubrutinib for inhibiting Bruton’s tyrosine kinase (BTK) produced significantly longer progression-free survival in comparison with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), researchers report. The use of zanubrutinib was also associated with fewer cardiac adverse events.

In the final analysis of a multinational, randomized, phase 3, head-to-head trial of zanubrutinib and ibrutinib, these results are reported for a primary endpoint of overall response and a key secondary endpoint of progression-free survival: “At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P = 0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.”

Source: New England Journal of Medicine