Acalabrutinib in TN and R/R WM: 5-year phase II study results

Results from the 5-year follow-up of the open-label, multicenter, single-arm, phase II ACE-WM-001 study (NCT02180724), evaluating acalabrutinib monotherapy in patients with treatment-naïve (TN; n = 14) or relapsed/refractory (R/R; n = 92) Waldenström macroglobulinemia (WM), were published in Blood Advances by Owen et al. The primary endpoint was investigator-assessed overall response rate (ORR). Key secondary endpoints included investigator-assessed duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

Key data: The ORR was 92.9% (95% confidence interval [CI], 66.1–99.8) in the TN cohort and 94.6% (95% CI, 87.8–98.2) in the R/R cohort, with a partial response or better demonstrated in 78.6% and 81.5% of patients, respectively. The median PFS, DoR, and OS were not reached (NR) in the TN cohort and were 67.5 months, 64.7 months, and NR, respectively, in the R/R cohort. Overall, Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 62.3% of patients and most commonly included neutropenia (17.0%), pneumonia (9.4%), lower respiratory tract infection (LRTI; 6.6%), and anemia (5.7%). Events of clinical interest (any grade; Grade 3–4) included atrial fibrillation/flutter (11.3%; 1.9%), bleeding events (62.3%; 5.7%), and hypertension (6.6%; 3.8%).

Key learning: Results suggest that long-term acalabrutinib monotherapy provides durable efficacy with no new toxicities and a low cardiovascular event rate, supporting its potential role in TN and R/R WM management.