A real-world comparative analysis of cardiovascular (CV) safety and time to next treatment (TTNT) with acalabrutinib versus ibrutinib in treatment-naive patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

e23280 Background: Bruton tyrosine kinase inhibitors (BTKis) are standard of care in CLL/SLL. However, BTKis, especially ibrutinib, are associated with CV toxicities that can affect the relative dose intensity and duration of therapy. This real-world analysis compared the frequency of CV adverse events and explored TTNT in treatment-naive patients with CLL/SLL receiving acalabrutinib or ibrutinib monotherapy in US clinical practice. Methods: This retrospective, observational study used electronic medical record data from ONCare Alliance, a network of 32 US community oncology/hematology practices. The study included patients with treatment-naive CLL/SLL initiating either acalabrutinib or ibrutinib monotherapy on or between 1/1/2017 and 12/31/2023. Data collected included patient and disease characteristics, CV medical events of interest (MEOI), and TTNT, calculated as the time from the start of therapy to the next treatment. Endpoints were evaluated using propensity score-weighted Kaplan-Meier analysis and Cox proportional hazards multivariate analysis. A sensitivity analysis was conducted to evaluate the stability of the primary findings. Results: The analysis included 454 patients (227 per treatment group). Baseline characteristics of patients in the acalabrutinib and ibrutinib cohorts were generally well balanced, with respect to median age (72 vs 73 years) and history of hypertension (HTN) (67.8% vs 66.5%). After a median follow-up of 28 months, the proportion of patients with CV MEOI was lower in the acalabrutinib cohort than in the ibrutinib cohort (20.3% vs 45.8%; p < 0.001). The median time to first CV MEOI was not reached (95% confidence interval [CI] 34.5–not reached [NR] months) with acalabrutinib versus 44.8 months (95% CI 8.2–NR) with ibrutinib (hazard ratio 0.47; 95% CI 0.33–0.68; p < 0.001).Specific MEOIs were generally less common with acalabrutinib than with ibrutinib, including new/worsening HTN, atrial fibrillation, clinically significant bleeding events, cardiac arrhythmia, and ventricular arrhythmia. Median TTNT in the acalabrutinib cohort was 48.2 months (95% CI 41.8–NR) and in the ibrutinib cohort was 30.7 months (95% CI 9.8–NR). Conclusions: In this retrospective real-world data analysis comparing acalabrutinib with ibrutinib in the first-line setting, treatment-naive patients with CLL/SLL receiving acalabrutinib had fewer CV safety events and continued to receive treatment for longer than those receiving ibrutinib.