Real-world comparative effectiveness of acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia

Novel agents, including Bruton tyrosine kinase inhibitors (BTKis), have become the standard of care for patients with chronic lymphocytic leukemia (CLL). We conducted a real-world retrospective analysis of patients with CLL treated with acalabrutinib vs ibrutinib using the Flatiron Health database. Patients with CLL were included if they initiated acalabrutinib or ibrutinib between 1 January 2018 and 28 February 2021. The primary outcome of interest was time to treatment discontinuation (TTD). Kaplan-Meier analysis was used to estimate unweighted and weighted median TTD. A weighted Cox proportional hazards model was used to compare the TTD between cohorts. Of the 2509 patients included in the analysis, 89.6% received ibrutinib, and 14.1% received acalabrutinib. TTD was not significantly different between cohorts in the unweighted analysis. After weighting, the cohorts were balanced on all baseline characteristics except cardiovascular risk factors and baseline medications use. The median (95% confidence interval [CI]) TTD was not reached (NR; 95% CI, 25.1 to NR) for the acalabrutinib cohort and was 23.4 months (95% CI, 18.1-28.7) for the ibrutinib cohort. The discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort vs 31% for the weighted ibrutinib cohort (P = .005). After additional adjustment for prior BTKi use, the acalabrutinib cohort had a 41% lower risk of discontinuation vs ibrutinib (hazard ratio, 0.59; 95% CI, 0.43-0.81; P = .001). In the largest available study comparing BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs those receiving ibrutinib.