Roger G. Owen, H. McCarthy, Shirley D’Sa, Sheeba K. Thomas, Olivier Tournilhac, Francesco Forconi, Marie José Kersten, Pier Luigi Zinzani, Sunil Iyengar, Jaimal Kothari, Monique C. Minnema, Efstathios Kastritis, Bruce David Cheson, Harriet Sarah Walter, Daniel Greenwald, Roser Calvo, Yi Li, Simon Rule, Richard R. Furman
ABSTRACT: Acalabrutinib is a covalent Bruton tyrosine kinase inhibitor. In the phase 2 ACE-WM-001 trial, at 27.4-month median follow-up, acalabrutinib yielded durable responses in patients with treatment-naive (TN) or relapsed/refractory (R/R) Waldenström macroglobulinemia (WM). We report WM-001 results at 63.7-month median follow-up. Overall, 106 patients (TN, n = 14; R/R, n = 92) were treated; 52.8% discontinued treatment (TN, n = 7; R/R, n = 49), most commonly because of disease progression (19.8%; TN, n = 1; R/R, n = 20) and adverse events (AEs; 17.9%; TN, n = 4; R/R, n = 15). Overall response rates were 92.9% and 94.6%, and major response rates (partial response or better) were 78.6% and 81.5% in the TN and R/R cohorts, respectively. Median progression-free survival (PFS) was not estimable (NE; 95% confidence interval, 19.3 to NE) and 67.5 months (53.3 to NE), with estimated 66-month PFS rates of 83.6% (48.0-95.7) and 52.0% (39.3-63.2) in the TN and R/R cohorts, respectively. Median duration of response (DOR) was not reached (NR) (11.9 months to NE) and 64.7 months (54.5 to NE), with estimated 66-month DOR rates of 90.0% (47.3-98.5) and 44.8% (27.1-61.1) in the TN and R/R cohorts, respectively. Median overall survival (OS) was NR in both cohorts; estimated 66-month OS rates were 90.9% (50.8-98.7) and 71.2% (60.3-79.6), respectively. Cardiac events of clinical interest occurred in 22 (20.8%) patients. One grade 5 AE (intracranial hematoma) was considered treatment related. With 5 years of follow-up, the efficacy and safety of acalabrutinib in WM were maintained. This trial was registered at www.clinicaltrials.gov as NCT02180724.