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

Presented by
Prof. Peter Hillmen, St James’s University Hospital, UK
EHA 2021
The phase 3, head-to-head ELEVATE-RR trial compared acalabrutinib versus ibrutinib in previously treated patients with chronic lymphocytic leukaemia (CLL). The first results indicate that acalabrutinib achieved better tolerability with fewer patients experiencing cardiovascular toxicities. Moreover, acalabrutinib had similar efficacy to ibrutinib.

Ibrutinib was the first irreversible Bruton’s tyrosine kinase (BTK) inhibitor but has been 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 safety outcomes results of the randomised, multicentre, open-label ELEVATE-RR trial (NCT02477696), which compared safety and efficacy of acalabrutinib and ibrutinib in patients (n=533) with previously treated CLL and presence of del(17p) or del(11q) (median age 66 years) [1]. Patients were randomised 1:1 to receive either 100 mg acalabrutinib twice daily (n=268) or 420 mg ibrutinib once daily (n=265). The primary endpoint was non-inferiority in progression-free survival (PFS).

With a median follow-up of 40.9 months (0.0–59.1 months), median PFS was 38.4 months in both arms. Thus, the primary endpoint of non-inferiority of PFS with acalabrutinib versus ibrutinib was met (HR 1.00; 95% CI 0.79–1.27).

More than half of the patients discontinued treatment (52.6% in the acalabrutinib arm vs 58.5% in the ibrutinib arm), mainly due to disease progression. The first safety outcomes of the secondary endpoints showed a significantly lower incidence of atrial fibrillation/flutter with acalabrutinib (P=0.02; see Figure), the incidence of grade ≥3 infection was similar (P=0.88), the incidence of Richter’s transformation was comparable (3.8% with acalabrutinib vs 4.9% with ibrutinib). Overall survival showed an initial 18% benefit for acalabrutinib (HR 0.82; 95% CI 0.59–1.15). Summarising safety data revealed fewer AEs leading to treatment discontinuation (14.7% with acalabrutinib vs 21.3% with ibrutinib), fewer deaths due to AEs for acalabrutinib (6.4% vs 9.5%, respectively), while any-grade and grade ≥3 AEs incidences were comparable (97.7% vs 97.3%; 68.8% vs 74.9%).

Figure: Incidence of atrial fibrillation and flutter in the ELEVATE-RR trial [1]

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 Virtual Congress, 9–17 June.


Want to read more? Medicom has a featured interview with Dr John Byrd (Ohio State University College of Medicine, OH, USA) about the ELEVATE-RR trial: Acalabrutinib demonstrates similar efficacy and better safety compared with ibrutinib.

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