Acalabrutinib vs chlorambucil plus rituximab in untreated chronic lymphocytic leukemia: A randomized phase 3 Asian study.

Acalabrutinib is a selective, covalent Bruton tyrosine kinase inhibitor approved in multiple countries for patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is approved in China for patients with CLL who received ≥ 1 prior therapy. We report results from a randomized, multicenter, open-label, phase 3 study (NCT04075292) evaluating the efficacy and safety of acalabrutinib vs chlorambucil plus rituximab (C + R) in medically unfit patients with treatment-naive CLL in Asia. As of January 3, 2024, 155 patients (overall cohort: acalabrutinib, n = 77; C + R, n = 78; China cohort [mainland China and Taiwan], n = 53 and n = 50, respectively) were enrolled. With a median follow-up of 23.5 and 18.2 months in the overall and China cohorts, respectively, acalabrutinib demonstrated a 92% risk reduction of disease progression or death vs C + R (both cohorts: hazard ratio, 0.08; P < 0.0001; primary endpoint). Overall response rates were 76.6% vs 71.8% with median duration of response not reached vs 11.6 months in the acalabrutinib vs C + R arms, respectively. In the acalabrutinib arm, no atrial fibrillation or hypertension events were observed. Efficacy and safety were consistent across cohorts. Acalabrutinib was well tolerated and demonstrated a progression-free survival benefit vs C + R in this Asian population.