Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: Acalabrutinib is a selective, covalent Bruton tyrosine kinase inhibitor approved for marketing in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report final, long-term phase 1/2 study results in 99 patients with treatment-naive (TN) and 134 with relapsed/refractory (R/R) CLL/SLL. At final data cutoff, 71% and 31% of patients in the TN and R/R cohorts, respectively, remained on acalabrutinib treatment (median follow-up of 73.7 and 52.6 months). Among the events of clinical interest (any grade) in the TN and R/R cohorts, atrial fibrillation was reported in 6.1% and 9.0%, hypertension in 29.3% and 23.1%, other malignancies (excluding nonmelanoma skin cancer) in 14.1% and 17.2%, and major bleeding in 8.1% and 8.2% of patients, respectively. The incidence of the most common adverse events decreased over time. Overall response rates were 97.0% and 94.8% in the TN and R/R cohorts, respectively, with similar response findings among patients with standard and high-risk genomic features. In the TN cohort, median progression-free survival (PFS) was not reached and the 72-month PFS rate was 86.7% (95% confidence interval [CI], 77.0-92.5). For the R/R cohort, median PFS was 66.1 months (range, 0.4-87.8) and the 72-month PFS rate was 45.1% (95% CI, 35.6-54.1). This final analysis extends the duration of benefit observed with acalabrutinib, demonstrates that no new safety signals are apparent with longer follow-up, and confirms the safety and tolerability of acalabrutinib monotherapy for patients with CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02029443.
Source: Blood Advances
Authors: Richard R. Furman, William G. Wierda, Piers E. M. Patten, Jorge M. Chaves, Jennifer R. Brown, Talha Munir, Peter Martin, Farrukh T. Awan, Deborah M. Stephens, Paolo Ghia, Jacqueline C. Barrientos, Krish Patel, Jennifer A. Woyach, Marianne de Borja, Min-Hui Wang, Nitin Jain, Susan M. O’Brien, John C. Byrd
Institutions: NewYork–Presbyterian Hospital, Cornell University, Weill Cornell Medicine, The University of Texas MD Anderson Cancer Center, King's College London, King's College Hospital, Northwest Medical Specialties, Dana-Farber Cancer Institute, St James's University Hospital, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Hofstra University, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, The Ohio State University, AstraZeneca (Canada), AstraZeneca (United States), University of California, Irvine
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: AstraZeneca, University of Oxford
OpenAlex ID: W7147021037