Differential cardiotoxicity of acalabrutinib versus chemoimmunotherapy in chronic lymphocytic leukemia: A retrospective cohort study from 2000-2025 using TriNetX database.

e19022 Background: Chronic lymphocytic leukemia (CLL) is a common adult leukemia that originates by dysfunctional development of the lymphocytes. Acalabrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, has demonstrated promising outcomes as a targeted therapy alternative to chemoimmunotherapy for treating CLL. The objective of this retrospective analysis was to compare the safety profiles of acalabrutinib and chemoimmunotherapy in patients with CLL and to evaluate the potential of acalabrutinib as an alternative therapeutic option. Methods: We conducted a retrospective cohort analysis using the TriNetX platform analyzing data of patients diagnosed with CLL from January, 2000 to January, 2025. Data was classified into cohorts on the basis of treatment with either acalabrutinib or chemoimmunotherapy. Propensity score matching analysis was carried out to balance their demographic and clinical characteristics. Demographic factors included age (≥18 years), sex, race, and ethnicity. Outcomes assessed included all cause death, atrial fibrillation, hypertension, acute heart failure, ventricular arrythmias, and bleeding. Kaplan-Meier survival analysis was employed. Results: A total of 4,006 patients were included in the analysis, 847 received acalabrutinib and 3,172 underwent chemoimmunotherapy, with a mean age of 70±11 and 69±14 years respectively. Participants were mostly male, with the majority of the patients being non-Hispanic Whites. Median period of follow up was 578 and 925 days respectively, incidence and risk of mortality and adverse events were assessed. A lower risk of mortality was noted with acalabrutinib (RR: 0.407; 95%CI: 0.32, 0.51; p<0.0001). Additionally, atrial fibrillation developed in fewer than 10 patients on use of acalabrutinib, thus carrying significantly lower odds (odds ratio (OR):0.3; 95%CI: 0.16, 0.58; p=0.001) than chemoimmunotherapy, which reported atrial fibrillation in 120 patients. Similarly, significantly lesser incidence of hypertension was noted on use of acalabrutinib, implying safer drug profile. Bleeding risk was also reduced in the acalabrutinib cohort and was statistically significant (OR:0.36, 95%CI: 0.24, 0.52; p<0.0001). The odds of acute heart failure (OR:1.25, 95%CI: 0.61, 2.57; p=0.54) and ventricular arrhythmia (OR:1.5, 95%CI: 0.72, 3.14; p=0.2) were statistically nonsignificant. Conclusions: The use of acalabrutinib in patients with CLL was associated with statistically significant better safety profile, with lesser risk of mortality, bleeding events and atrial fibrillation. Clinicians may consider using acalabrutinib as a superior treatment modality in the treatment of CLL. Further research maybe required to optimize treatment protocols in the best interest of patients.