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

Abstract

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 CLL patients treated with acalabrutinib vs ibrutinib to compare outcomes utilizing the Flatiron Health Database. Patients with CLL were included if they initiated acalabrutinib or ibrutinib between 1/1/2018-2/28/2021. The primary outcome of interest was time to treatment discontinuation (TTD). Average treatment effect among the treated weighting was used to balance key baseline characteristics between cohorts. Kaplan-Meier analysis was used to estimate unweighted and weighted median TTD. A weighted Cox proportional-hazards model was used to compare TTD between cohorts. Out of 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% CI) TTD was not reached (NR; 25.1, NR) for the acalabrutinib cohort and was 23.4 months (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 adjustments for prior BTKi use, the acalabrutinib cohort had a 41% lower risk of discontinuation vs. ibrutinib (HR 0.59; 0.43, 0.81; P = .001). In the largest available study comparing two BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs ibrutinib.

Real-World Outcome of Treatment with Single-Agent Ibrutinib in Italian Patients with Chronic Lymphocytic Leukemia: Final Results of the EVIdeNCE Study

“…The most common reason for treatment discontinuation was AE/toxicity. This observation is in line with the majority of real-world studies that identified AEs as the main reason for discontinuing ibrutinib [ 18 , 24 , 26 , 27 , 28 , 29 , 41 ] and possibly other BTKi [ 43 ]. Conversely, disease progression was the most frequent cause of treatment discontinuation recorded in RTCs.…”

Three-year cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia or small cell lymphocytic lymphoma treated with Bruton tyrosine kinase inhibitors acalabrutinib or ibrutinib: a real-world analysis

“…Our study has strengths such as an expressive sample size and the real-world characteristics of the data. Although other real-word analyses have been conducted between acalabrutinib versus ibrutinib, they focused on the cancer treatment effectiveness such as time to treatment discontinuation (22), differently from us that focused on cardiovascular and non-cardiovascular safety in patients with rstline therapy However, we should recognize several limitations. First, the analysis was retrospective, which can lead to selection bias when analyzing treatment arms.…”

Challenges associated with the use of Bruton's tyrosine kinase inhibitors: A life‑saving therapy for chronic lymphocytic leukemia (Review)

“…Acalabrutinib has been approved for CLL therapy and has an efficacy comparable to that of ibrutinib, although with fewer AEs (34). As a result, is was previously demonstrated that patients who received acalabrutinib had a 41% lower risk of discontinuation and a longer time to discontinuation compared to those treated with ibrutinib (35). Acalabrutinib monotherapy given in treatment-naïve patients with CLL was found to be cost-effective compared to chlorambucil + obinutuzumab (36).…”