Estimated cardiac deaths associated with treating chronic lymphocytic leukemia with ibrutinib versus zanubrutinib in the United States.

backgroundIn the absence of real-world comparative studies of cardiac death risk, this study estimates the potential reduction in cardiac mortality associated with treating chronic lymphocytic leukemia (CLL) patients with zanubrutinib instead of ibrutinib in first-line (1L) or second-line or later (2L+) in the United States (US).

methodsNumber needed to treat (NNT) for incremental cardiac death with ibrutinib versus zanubrutinib was applied to real-world ibrutinib utilization from Symphony over 5 years (2020-2024). Primary analysis utilized head-to-head cardiac death risks from ALPINE (2L+). An exploratory 1L analysis utilized indirect comparisons from SEQUOIA and RESONATE-2. Sensitivity analyses assessed cardiac death risk with 10+ years of ibrutinib utilization (2014-2024).

resultsIn 2L+ CLL, NNT for incremental cardiac death was 54 patients. Based on real-world ibrutinib use, 81 cardiac deaths could potentially have been avoided with zanubrutinib over 5 years. The exploratory 1L CLL NNT per cardiac death was 46, corresponding to 140 potentially avoidable deaths if patients were treated with zanubrutinib. Over a 10+ year period, the number of potentially avoidable deaths increased to 318 (2L+) and 489 (1L).

conclusionsThe NNT model suggests substantial cardiac death reductions if zanubrutinib were utilized instead of ibrutinib for CLL treatment in US practice.