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Comparing BTKis Acalabrutinib and Ibrutinib in Real-World Analysis of Patients With CLL
Bruton’s Tyrosine Kinase inhibitors (BTKi) such as ibrutinib and acalabrutinib have become the standard-of-care treatment for patients with chronic lymphocytic leukemia (CLL). The recent ELEVATE-RR trial (NCT02477696) compared the two BTKis and showed that patients with relapsed/refractory CLL treated with acalabrutinib showed noninferior progression-free survival (PFS) with fewer cardiovascular (CV) and bleeding adverse events compared with those treated with ibrutinib.
At the 2022 American Society of Hematology Annual Meeting and Exposition, Lindsey E Roeker, MD, and colleagues shared outcomes of a real-world analysis of patients with CLL treated with acalabrutinib vs ibrutinib in their poster presentation, “Comparing acalabrutinib and ibrutinib in the real world: A study of 2,509 patients with chronic lymphocytic leukemia.”
“We know that demographic and clinical characteristics of patients treated in the real-world clinical practice often differ than those treated in clinical trials,” Dr Roeker said. “And differences in outcomes may be observed. Given these potential differences, we performed this study to understand differences between these drugs in the real-world setting.”
Utilizing electronic health record data from July 2017 to February 2021 from the Flatiron Health Database, the retrospective cohort study included patients with CLL or small lymphocytic lymphoma (SLL) who had initiated acalabrutinib or ibrutinib in any line of therapy (LOT) as of January 1, 2018. Time to treatment discontinuation (TTD) was defined as the time from the initiation of treatment to discontinuation (ie, start of a new LOT, lack of refilled prescription for ≥3 months, or death).
Average treatment effect among the treated (ATT) weighting balanced key baseline characteristics (age, sex, race, geographic region, year of index date, year of diagnosis with CLL or SLL, line of therapy, Rai stage, modified Quan-CCI score, atrial fibrillation, ECOG performance status, and use of anticoagulants) and improved cohort comparability.
A total of 2,509 patients matched the criteria and were included in the analysis; 2,249 patients (89.6%) received ibrutinib and 353 (14.1%) received acalabrutinib across LOTs. Median age at drug initiation of the acalabrutinib vs the ibrutinib arm was 73.0 years vs 72.0 years, respectively, and sex and race were similar in both cohorts.
With a median follow-up of 15.9 months for the entire cohort, the TTD of patients in the acalabrutinib arm compared to those in the ibrutinib cohort was significantly longer in the weighted analysis of all patients. The median unweighted TTD was not reached (NR; 95% confidence interval [CI]: 25.1, NR) in patients receiving acalabrutinib, and was 29.3 months (95% CI: 27.7, 33.2) in the ibrutinib group. The median weighted TTD for the acalabrutinib group was also NR (25.1, NR), compared to 23.4 months (18.1, 28.7) for patients treated with ibrutinib.
Discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort and 31% for patients in the weighted ibrutinib cohort (P = .005). After adjusting 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). When stratified by LOT, results showed a consistent trend toward superior TTD in the acalabrutinib cohort.
“This study is the largest available analysis comparing two BTK inhibitors to date, and suggests lower rates of discontinuation and a prolonged time to discontinuation for patients receiving acalabrutinib as compared to ibrutinib in both the front-line and relapsed/refractory settings,” Dr Roeker said. “While randomized clinical trial data have compared patients treated with acalabrutinib to ibrutinib in the relapsed/refractory setting, these data provide valuable insight into how these agents compare in the front-line setting, which was specifically not tested in the ELEVATE-RR trial, as well as outcomes in clinical practice across treatment lines outside of the trial setting.”
Additional analyses with longer follow-up are required to confirm the study findings, the authors concluded, and to determine if an improved TTD is associated with improved PFS and overall survival outcomes.
Roeker L, DerSarkissian M, Ryan K, et al. Comparing acalabrutinib and ibrutinib in the real world: A study of 2,509 patients with chronic lymphocytic leukemia. Presented at: 64th ASH Annual Meeting and Exposition. December 10-13, 2022. Abstract 1808.
