Real-World Comparison of ACP-196 and Ibrutinib in CLL Treatment

For individuals with chronic lymphocytic leukemia (CLL), novel medicines such as Bruton Tyrosine Kinase inhibitors (BTKi) have established themselves as first-line therapy. Patients with relapsed or refractory CLL who were treated with acalabrutinib had a non-inferior progression-free survival (PFS) and a lower risk of cardiovascular (CV) and bleeding side events than those treated with ibrutinib, according to the ELEVATE-RR study (NCT02477696). However, when comparing clinical practice to clinical trials, it is important to remember that outcome discrepancies are possible due to the wide variety of features and management approaches used in each setting. To assess outcomes in a non-trial population, researchers conducted a real-world analysis of CLL patients treated with acalabrutinib versus ibrutinib.

From July 2017 through February 2021, a retrospective cohort study used data from the Flatiron Health Database’s electronic health records. Individuals with CLL or small lymphocytic lymphoma (SLL) who started acalabrutinib or ibrutinib in any line of therapy (LOT) on or after January 1, 2018, were included. Data collection ended on February 28, 2021, or at the earliest possible time when patients were no longer being followed. Time to treatment discontinuation (TTD) was defined as the time between the first day of treatment and the first day of a new LOT, the first refill in more than three months, or the patient’s death. At the end of the follow-up period, patients who had continued to take BTKi were considered censored.

Key baseline characteristics (age, sex, race, geographic region, index date, year of diagnosis of CLL or SLL, line of therapy, Rai stage, modified Quan-CCI score, atrial fibrillation, ECOG performance status, and use of anti-coagulants) were weighted using the average treatment effect among the treated (ATT) method to ensure comparability between the cohorts. Weighted and unweighted TTD estimates were calculated using Kaplan-Meier analysis. Calabrutinib and ibrutinib were compared to TTD using a weighted Cox proportional hazards (PH) model.

A total of 2,509 patients were found and included in the analysis between January 2018 and February 2021. In all lines of therapy, 89.6% (n=2,249) of these patients were given ibrutinib, whereas 14.1% (n=353) were given acalabrutinib. The median age at the drug beginning for the acalabrutinib cohort was 73.0 years, while for the ibrutinib cohort, it was 72.0 years. The cohorts had comparable sex and racial makeups. The baseline characteristics were similar in the acalabrutinib and ibrutinib cohorts after being weighted to account for significant differences between the two groups; the ibrutinib cohort, however, had a higher prevalence of CV risk factors and past BTKi usage (more common in the acalabrutinib cohort; Table 1). One covariate in the Cox PH model is previous BTKi use.

TTD for acalabrutinib was much longer than ibrutinib in the weighted analysis of all patients, with a median follow-up of 15.9 months for the entire sample. In the acalabrutinib cohort, the median unweighted TTD was not reached (not reached [NR]) (95% CI: 25.1, NR), but in the ibrutinib group, the median TTD was achieved (29.3 months; 27.7, 33.2). Weighting did not change the median TTD for the acalabrutinib cohort, which remained at NR (25.1, NR), whereas the median TTD for the ibrutinib group increased to 23.4 months (18.1, 28.7). At 12 months, the weighted acalabrutinib group had a 22% discontinuation rate, while the weighted ibrutinib cohort had a 31% discontinuation rate (p=0.005). Further adjustments for prior BTKi treatment revealed a 41% reduction in discontinuation in the acalabrutinib sample compared to ibrutinib (HR 0.59; 0.43, 0.81; p=0.001). When the data was broken down further by LOT, they saw that acalabrutinib consistently had a better TTD than the control group.

Based on the greatest available experience comparing two BTKis, the authors conclude that acalabrutinib is superior to ibrutinib in both the first-line and relapsed/refractory situations, with patients using it seeing a lower rate of discontinuation and a longer time to discontinuation. These data provide valuable insight into how these agents compare in the front-line setting (not tested in ELEVATE-RR) and outcomes in clinical practice outside the trial setting, despite randomized data demonstrating similar PFS for patients treated with acalabrutinib and ibrutinib in the relapsed/refractory setting. Information to be presented includes the rationale behind the withdrawal of each medication, the results of expanded follow-up with the original sample, and a comparison based on the molecular genetic profiles that were already collected.

Source: https://ash.confex.com/ash/2022/webprogram/Paper167213.html

Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02477696

Roeker, L., DerSarkissian M, Ryan K, Chen Y, Wahlstrom S, Hakre S, Yu L, Guo H, and Mato A (2022). Comparing Acalabrutinib and Ibrutinib in the Real World: A Study of 2,509 Patients with Chronic Lymphocytic Leukemia. [online] ash.confex.com. Available at: https://ash.confex.com/ash/2022/webprogram/Paper167213.html [Accessed 20 Feb. 2023].