Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia.
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All Authors
Furman, RR.
Wierda, WG.
Patten, PE.
Chaves, JM.
Brown, JR.
Munir, T.
Martin, P.
Awan, FT.
Stephens, DM.
Ghia, P.
LTHT Author
Munir, Talha
LTHT Department
Oncology
Haematology
Haematology
Non Medic
Publication Date
2026
Item Type
Journal Article
Language
Subject
LEUKAEMIA , LYMPHOCYTIC , CHRONIC , B-CELL , ANTINEOPLASTIC AGENTS
Subject Headings
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 (NCT02029443) 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 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 non-melanoma 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 seen with acalabrutinib, demonstrates that no new safety signals are apparent with longer follow-up, and confirms the safety and tolerability of acalabrutinib monotherapy in patients with CLL/SLL.
Journal
Blood Advances