Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor approved in the United States and Europe for chronic lymphocytic leukemia (CLL) based on phase 3 trials with limited representation of Asian populations. This phase 1/2 trial evaluates acalabrutinib in Chinese adults with relapsed/refractory (R/R) CLL receiving acalabrutinib 100 mg twice daily in 28-day cycles until disease progression or treatment discontinuation due to adverse events (AEs) presenting substantial clinical risk. The primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). A total of 60 patients from 20 sites in China received acalabrutinib (median age 62 years; median 1 prior therapy line; 21.7% with del(17p) and/or TP53 mutation; 51.7% with unmutated IGHV). Median total treatment duration was 19.4 months (range 0.6-28.2) with 53 patients (88.3%) receiving acalabrutinib at data cutoff; median study follow-up was 20.2 months. BICR-assessed ORR was 85.0% (95% CI, 73.4-92.9). Median duration of response, progression-free survival (PFS), and overall survival (OS) were not reached. Estimated 12-month and 18-month PFS rates were 91.5% (95% CI, 80.9-96.4) and 78.8% (95% CI, 60.9-89.2); OS rates were both 96.7% (95% CI, 87.3-99.2). AEs of grade ≥ 3 occurred in 25 patients (41.7%), most commonly decreased neutrophil count (13.3%, n = 8), pneumonia (6.7%, n = 4), and upper respiratory tract infection (6.7%, n = 4). AEs led to treatment discontinuation in 2 patients (paraneoplastic pemphigus; rectal neoplasm). This study demonstrated high ORR in acalabrutinib-treated Chinese patients with R/R CLL with no unexpected safety concerns. This trial is registered on ClinicalTrials.gov (NCT03932331).