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 (NCT02180724), at 27.4 months 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 months 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 due to 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) were 78.6% and 81.5% in the TN and R/R cohorts, respectively. Median progression-free survival (PFS) was not estimable (NE; 95% CI: 19.3, NE) and 67.5 months (53.3, 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, NE) and 64.7 months (54.5, 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, efficacy and safety of acalabrutinib in WM were maintained.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2026-04-15
DOI
https://doi.org/10.1182/bloodadvances.2025017713
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Sheeba K. Thomas, Shirley D’Sa, Richard R. Furman, H. McCarthy et al.
Blood Advances
Chronic Lymphocytic Leukemia Research
article

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

Sheeba K. Thomas, Shirley D’Sa, Richard R. Furman, H. McCarthy, Marie José Kersten, Sunil Iyengar, Monique C. Minnema, Olivier Tournilhac, Roger G. Owen, Francesco Forconi, Pier Luigi Zinzani, Jaimal Kothari, Roser Calvo, Simon Rule, Harriet Sarah Walter, Yi Li, Efstathios Kastritis, Daniel Greenwald, Bruce David Cheson
article en

Abstract

Acalabrutinib is a covalent Bruton tyrosine kinase inhibitor. In the phase 2 ACE-WM-001 trial (NCT02180724), at 27.4 months 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 months 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 due to 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) were 78.6% and 81.5% in the TN and R/R cohorts, respectively. Median progression-free survival (PFS) was not estimable (NE; 95% CI: 19.3, NE) and 67.5 months (53.3, 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, NE) and 64.7 months (54.5, 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, efficacy and safety of acalabrutinib in WM were maintained.

Blood Advances
AstraZeneca (United Kingdom) (GB), Santa Barbara City College (US), University College London Hospitals NHS Foundation Trust (GB), The University of Texas MD Anderson Cancer Center (US), Institute of Cancer Research (GB), University of Leicester (GB), University of California, Santa Barbara (US), National and Kapodistrian University of Athens (GR), Cornell University (US), Leeds Teaching Hospitals NHS Trust (GB), Royal Bournemouth Hospital (GB), University Medical Center Utrecht (NL), University of Clermont Auvergne (FR), Azienda USL di Bologna (IT), Royal Marsden Hospital (GB), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Oxford University Hospitals NHS Trust (GB), AstraZeneca (United States) (US), Amsterdam University Medical Centers (NL), University of Southampton (GB), University College London (GB)
Openalex Percentile: Top 20%
Chronic Lymphocytic Leukemia Research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.