ELEVATE-RR: Acalabrutinib demonstrates similar efficacy and better safety compared with ibrutinib

The phase 3 ELEVATE-RR trial was a head-to-head comparison of acalabrutinib versus ibrutinib in previously treated patients with chronic lymphocytic leukaemia. The first results of this study demonstrated that acalabrutinib had better tolerability than ibrutinib with fewer patients experiencing cardiovascular toxicities. Moreover, acalabrutinib had similar efficacy to ibrutinib concerning progression-free survival.

Bruton’s tyrosine kinase (BTK) plays a critical role in chronic lymphocytic leukaemia (CLL) tumour cell migration, adhesion, proliferation, and survival. Ibrutinib was the 1^st irreversible BTK inhibitor but is associated with adverse events (AEs), particularly cardiovascular toxicities, that can lead to treatment discontinuation. Acalabrutinib is a next-generation, more selective BTK inhibitor.

Prof. Peter Hillmen (St James’s University Hospital, UK) reported the first results of the head-to-head phase 3 trial ELEVATE-RR (NCT02477696), which compared safety and efficacy of ibrutinib and acalabrutinib in patients with previously treated CLL and presence of del(17p) or del(11q) [1]. Patients were randomised 1:1 into 2 treatment arms and received either 100 mg acalubritinib twice daily or 420 mg ibrutinib once daily. The primary endpoint was non-inferiority on progression-free survival (PFS), which was then followed by superiority analysis in secondary endpoints of safety and efficacy.

Included were 533 patients, 268 received acalabrutinib and 265 received ibrutinib. The median duration of follow up was 40.9 months. More than half of the patients discontinued treatment, mainly due to disease progression, which was to be expected given that the patients were pre-treated. Median PFS was 38.4 months in both arms. Thus, the primary endpoint, non-inferiority of PFS with acalabrutinib versus ibrutinib, was met.

First results of secondary endpoints were also presented: the incidence of any-grade atrial fibrillation/flutter was significantly lower with acalabrutinib, the incidence of grade ≥3 infection was similar between treatment arms, the incidence of Richter’s transformation was similar, and the hazard ratio of overall survival was comparable. Summarising safety data revealed fewer AEs leading to treatment discontinuation and fewer deaths due to AEs for acalabrutinib, while any-grade and grade ≥3 AE incidences were comparable.

Prof. Hillmen concluded, “Acalabrutinib was non-inferior to ibrutinib in the primary endpoint PFS and demonstrated lower frequencies of common AEs. These results demonstrate that acalabrutinib is better tolerated and has similar efficacy to ibrutinib in patients with previously treated CLL.”

1. Hillmen P et al. First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukaemia. P409-1, EHA 2021 Congress, 09–17 June.

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Posted on 16 June 20215 August 2021