Acalabrutinib versus investigator's choice in relapsed/refractory chronic lymphocytic leukemia: final ASCEND trial results.

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Authors
Jacob, Abraham
Issue Date
2022-11-14
Journal
Type
Clinical Trial
Multicentre Study
Peer-Reviewed Publication
Randomised Control Trial
Keywords
Leukemia
Chronic lymphocytic leukemia (CLL)
Acalabrutinib
Relapse
Ibrutinib
Cardiovascular toxicity
Bruton tyrosine kinase
Inhibitors
Refractory
Journal Title
HemaSphere
Volume
6
Issue
12
Begin page
e801
End page
Abstract
Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator's choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator's choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.
Citation
Ghia P, Pluta A, Wach M, Lysak D, Šimkovič M, Kriachok I, Illés Á, de la Serna J, Dolan S, Campbell P, Musuraca G, Jacob A, Avery EJ, Lee JH, Usenko G, Wang MH, Yu T, Jurczak W. Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. Hemasphere. 2022 Nov 14;6(12):e801. doi: 10.1097/HS9.0000000000000801. PMID: 36398134; PMCID: PMC9666115.