A phase III study that evaluated progression-free survival (PFS) outcomes with acalabrutinib versus ibrutinib in patients with previously treated chronic lymphocytic leukemia (CLL) found that acalabrutinib was associated with lower incidence of cardiovascular-related toxicities.
The randomized, multicenter, open-label, non-inferiority ELEVATE-RR study was conducted by John Seymour, PhD, of the Peter MacCallum Cancer Centre & the Royal Melbourne Hospital in Australia, and colleagues and published in Blood.
Investigators enrolled 529 patients with CLL: 266 received acalabrutinib and 263 received ibrutinib. The primary endpoints of the study were adverse events (AEs) and events of clinical interest (ECIs) in addition to PFS.
Common AEs, including diarrhea, arthralgia, urinary tract infection, back pain, muscle spasms, and dyspepsia, were found to have significantly lower incidence rates in patients treated with acalabrutinib. The exposure-adjusted incidence rates were 1.5 to 4.1 times higher in the ibrutinib group for these AEs. Conversely, the incidence rates of headache and cough were more frequent in patients treated with acalabrutinib, exhibiting 1.6- and 1.2-fold higher exposure-adjusted incidence rates, respectively.
When assessing selected ECIs, ibrutinib exhibited a higher incidence of atrial fibrillation/flutter, hypertension, and bleeding compared with acalabrutinib. The exposure-adjusted incidence rates for these ECIs were 2.0-, 2.8-, and 1.6-fold higher, respectively, in the ibrutinib group. However, the overall incidence rates for cardiac events (based on the Medical Dictionary for Regulatory Activities system organ class) and infections were similar between the two treatment arms.
The rate of treatment discontinuation due to AEs was significantly lower for patients receiving acalabrutinib (hazard ratio, 0.62; 95% CI, 0.41-0.93).
According to the investigators, “A limitation of this analysis is its open-label study design, which may influence the reporting of more subjective AEs.”
“Overall, event-based analyses and AE burden scores demonstrated higher AE burden overall and specifically for atrial fibrillation, hypertension, and hemorrhage with ibrutinib vs acalabrutinib,” they concluded.
Seymour JF, Byrd JC, Ghia P, et al. Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial. Blood. 2023;142(8):687-699. doi:10.1182/blood.2022018818