Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial

Byrd, JC; Hillmen, P; Ghia, P; Kater, AP; Chanan-Khan, A; Furman, RR; O&#39;Brien, S; Yenerel, MN; Illes, A; Kay, N; Garcia-Marco, JA; Mato, A; Pinilla-Ibarz, J; Seymour, JF; Lepretre, S; Stilgenbauer, S; Robak, T; Rothbaum, W; Izumi, R; Hamdy, A; Patel, P; Higgins, K; Sohoni, S; Jurczak, W

Author(s): Byrd, JC; Hillmen, P; Ghia, P; Kater, AP; Chanan-Khan, A; Furman, RR; O'Brien, S; Yenerel, MN; Illes, A; Kay, N; Garcia-Marco, JA; Mato, A; Pinilla-Ibarz, J; Seymour, JF; Lepretre, S; Stilgenbauer, S; Robak, T; Rothbaum, W; Izumi, R; Hamdy, A; Patel, P; Higgins, K; Sohoni, S; Jurczak, W;
Details: Publication Year 2021-11-01,Volume 39,Issue #31,Page 3441-3452
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: PURPOSE: Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-label, randomized, noninferiority, phase III trial comparing acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia (CLL). METHODS: Patients with previously treated CLL with centrally confirmed del(17)(p13.1) or del(11)(q22.3) were randomly assigned to oral acalabrutinib 100 mg twice daily or ibrutinib 420 mg once daily until progression or unacceptable toxicity. The primary end point was independent review committee-assessed noninferiority of progression-free survival (PFS). RESULTS: Overall, 533 patients (acalabrutinib, n = 268; ibrutinib, n = 265) were randomly assigned. At the data cutoff, 124 (46.3%) acalabrutinib patients and 109 (41.1%) ibrutinib patients remained on treatment. After a median follow-up of 40.9 months, acalabrutinib was determined to be noninferior to ibrutinib with a median PFS of 38.4 months in both arms (95% CI acalabrutinib, 33.0 to 38.6 and ibrutinib, 33.0 to 41.6; hazard ratio: 1.00; 95% CI, 0.79 to 1.27). All-grade atrial fibrillation/atrial flutter incidence was significantly lower with acalabrutinib versus ibrutinib (9.4% v 16.0%; P = .02); among other selected secondary end points, grade 3 or higher infections (30.8% v 30.0%) and Richter transformations (3.8% v 4.9%) were comparable between groups and median overall survival was not reached in either arm (hazard ratio, 0.82; 95% CI, 0.59 to 1.15), with 63 (23.5%) deaths with acalabrutinib and 73 (27.5%) with ibrutinib. Treatment discontinuations because of adverse events occurred in 14.7% of acalabrutinib-treated patients and 21.3% of ibrutinib-treated patients. CONCLUSION: In this first direct comparison of less versus more selective Bruton's tyrosine kinase inhibitors in CLL, acalabrutinib demonstrated noninferior PFS with fewer cardiovascular adverse events.
Keywords: Adenine/administration & dosage/analogs & derivatives; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Benzamides/administration & dosage; Female; Follow-Up Studies; Humans; Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/pathology; Male; Middle Aged; Piperidines/administration & dosage; Prognosis; Prospective Studies; Pyrazines/administration & dosage; Survival Rate
Department(s): Haematology
PubMed ID: 34310172
Publisher's Version: https://doi.org/10.1200/JCO.21.01210
Open Access at Publisher's Site: https://doi.org/10.1200/JCO.21.01210
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-06-20 03:31:50

Last Modified: 2025-06-20 03:33:48