Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: 72-month PFS rate: 86.7% (TN), 45.1% (R/R)

• Primary Outcome: Progression-free survival: median not reached (TN), 66.1 months (R/R)

• Nnt Or Sensitivity: Overall response rates: 97.0% (TN), 94.8% (R/R)

• Confidence Interval: TN: 95% CI 77.0-92.5%; R/R: 95% CI 35.6-54.1%

Clinical Application

Oral therapy with manageable toxicity profile, suitable for outpatient management Acalabrutinib likely PBS-listed for CLL; aligns with current RACGP and haematology society guidelines for BTK inhibitor use in CLL management Adults with CLL/SLL, both treatment-naive and relapsed/refractory disease

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.

References

1. 1.Furman, R. R., Wierda, W. G., Patten, P. E. M., Chaves, J. M., Brown, J. R., Munir, T., Martin, P., Awan, F. T., Stephens, D. M., Ghia, P., Barrientos, J. C., Patel, K., Woyach, J. A., de Borja, M., Wang, M.-H., Jain, N., O'Brien, S. M., & Byrd, J. C. (2026). Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia. Blood Advances. https://doi.org/10.1182/bloodadvances.2025018310