Conference Coverage

Reduced Cardiotoxicity and Mortality With Acalabrutinib vs Chemoimmunotherapy in CLL

Anthony Calabro, MA

Key Highlights

  • Acalabrutinib was associated with a 60% lower risk of all-cause mortality compared with chemoimmunotherapy.
  • Risk of atrial fibrillation and bleeding events was significantly lower with acalabrutinib.
  • Rates of hypertension were also reduced in the acalabrutinib group.
  • No significant differences in acute heart failure or ventricular arrhythmia between treatment groups.

In a 25-year retrospective cohort study, patients with chronic lymphocytic leukemia (CLL) treated with acalabrutinib had significantly lower risks of mortality, atrial fibrillation, bleeding, and hypertension compared with those treated with chemoimmunotherapy. The relative risk of all-cause mortality was 0.407 (95% CI, 0.32-0.51; P < .0001) in the acalabrutinib group, and the odds of atrial fibrillation were markedly lower (OR, 0.3; 95% CI, 0.16-0.58; P = .001), with fewer than 10 cases reported compared with 120 in the chemoimmunotherapy group.

Although chemoimmunotherapy has long been a mainstay of treatment for patients with CLL, targeted agents such as acalabrutinib have emerged as promising alternatives. Given the cardiovascular toxicity concerns associated with both disease and treatment, this study aimed to evaluate the differential cardiotoxicity and safety profile of acalabrutinib relative to conventional regimens.

Researchers conducted a retrospective analysis using the TriNetX platform, identifying patients diagnosed with CLL from January 2000 through January 2025. Researchers included a total of 4006 patients, with 847 receiving acalabrutinib and 3172 treated with chemoimmunotherapy. Propensity score matching was performed to balance demographic and clinical characteristics, including age, sex, race, and ethnicity. Kaplan-Meier methods were used to assess survival, and outcomes evaluated included all-cause death, atrial fibrillation, hypertension, acute heart failure, ventricular arrhythmias, and bleeding.

Acalabrutinib was associated with a significantly lower risk of hypertension and bleeding (OR for bleeding, 0.36; 95% CI, 0.24-0.52; P < .0001). However, no significant differences were observed in the odds of acute heart failure (OR, 1.25; P = .54) or ventricular arrhythmias (OR, 1.5; P = .20). The median follow-up period was shorter in the acalabrutinib cohort (578 days) compared with the chemoimmunotherapy cohort (925 days), which may limit comparative longitudinal interpretation.

“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,” the authors concluded.

Reference:
Qadeer A, Aslam R, Khan A, et al. Differential cardiotoxicity of acalabrutinib versus chemoimmunotherapy in chronic lymphocytic leukemia: A retrospective cohort study from 2000–2025 using TriNetX database. Presented at: American Society of Clinical Oncology 2025 Annual Conference; May 30-June 3, 2025; Chicago, IL. Accessed June 4, 2025. https://ascopubs.org/doi/pdf/10.1200/JCO.2025.43.16_suppl.e19022.