Hypertension and time to treatment failure with acalabrutinib and ibrutinib in treatment-naïve CLL/SLL

Bruton tyrosine kinase inhibitors (BTKis) are standard therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The second-generation BTKi, acalabrutinib, has similar efficacy but a more favorable cardiovascular toxicity profile than the first-generation BTKi ibrutinib. This retrospective, observational, real-world study used electronic medical records from ONCare Alliance, a network of 32 US community oncology/hematology practices. Adults (N = 454) with treatment-naïve CLL/SLL who initiated acalabrutinib or ibrutinib monotherapy between January 2017 and December 2023 were included (n = 227 per group). Baseline characteristics were well balanced. The primary endpoint was time to new/worsening hypertension; the key secondary endpoint was time to treatment failure (TTF). After a median follow-up of 28 months, acalabrutinib had fewer discontinuations due to intolerability (19.4% vs 46.7%; p<.001), a significantly lower risk of new/worsening hypertension (HR 0.27; 95% CI, 0.14–0.55; p<.001), and prolonged TTF (HR 0.42; 95% CI, 0.31–0.56; p<.001) versus ibrutinib. Sensitivity analyses demonstrated stability in the findings.