A real-world comparative study of hypertension (HTN) and time to treatment failure (TTF) with acalabrutinib versus ibrutinib in treatment-naive Medicare-eligible patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

e23279 Background: Bruton tyrosine kinase inhibitors (BTKis)are standard of care in CLL/SLL, but are associated with cardiovascular (CV) toxicities, such as HTN, that can affect treatment dose intensity. These toxicities are especially important in the Medicare population, who are typically elderly with multiple pre-existing CV comorbidities. This real-world study compared the risk of HTN and TTF with acalabrutinib versus ibrutinib monotherapy in treatment-naive Medicare-eligible patients with CLL/SLL. Methods: This retrospective, observational study used electronic medical record data from ONCare Alliance, a network of 32 US community oncology/hematology practices, and consisted of Medicare-eligible patients with treatment-naive CLL/SLL who started acalabrutinib or ibrutinib monotherapy on or between 1/1/2017 and 12/31/2023. The primary endpoint was time to development of new HTN/worsening of pre-existing HTN, defined as the addition of an anti-HTN medication, a dose increase of a current anti-HTN medication, a dose modification/discontinuation of the BTKi due to high blood pressure, or a provider reporting new/worsening HTN. The secondary endpoint was TTF, defined as time from treatment start to discontinuation due to disease progression, drug intolerability, patient/provider choice, or death. Endpoints were evaluated using propensity score-weighted Kaplan-Meier and multivariate Cox proportional hazard regression analyses. Sensitivity analyses tested the stability of the primary endpoint. Results: 166 acalabrutinib- and 173 ibrutinib-treated Medicare-eligible patients aged ≥ 65 years were included. Baseline characteristics were well balanced between acalabrutinib and ibrutinib, with respect to median age (76 vs 75 years), ECOG performance status, and history of HTN (75.9% vs 73.4%). After a median follow-up of 28 months, drug discontinuations due to intolerability were less common with acalabrutinib than ibrutinib (22.9% vs 48.6%; p = 0.001). Acalabrutinib significantly reduced the risk of new/worsening HTN (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.09–0.53; p = 0.001) and improved TTF (HR 0.44; 95% CI 0.32–0.61; p = 0.001) versus ibrutinib. Other CV events were less common with acalabrutinib than ibrutinib. The sensitivity analyses indicated stability in the primary analysis results. Conclusions: In treatment-naive Medicare-eligible patients with CLL/SLL, acalabrutinib had fewer CV events, a lower risk of new/worsening HTN, fewer discontinuations due to intolerability, and prolonged TTF versus ibrutinib.