Acalabrutinib in Waldenström macroglobulinemia yields durable responses with 5 years of follow-up.

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.