Acalabrutinib Produces High ORR in Chinese Patients With R/R CLL

Chronic Lymphocytic Leukemia
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Acalabrutinib (Calquence) monotherapy generated high levels of activity in Chinese patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to findings from a phase 1/2 study (NCT03932331) published in Annals of Hematology.

At a median follow-up of 20.2 months (range, 1.1-28.2), the overall response rate (ORR) per blinded independent central review (BICR) among efficacy-evaluable patients who received acalabrutinib (n = 60) was 85.0% (95% CI, 73.4%-92.9%); all responses were partial. The median duration of response (DOR) was not yet reached (NR; 95% CI, not estimable [NE]-NE). The 12- and 18-month DOR rates were 90.1% (95% CI, 71.3%-96.8%) and 80.8% (95% CI, 58.8%-91.8%), respectively.

“This study aimed to determine whether the safety and efficacy of acalabrutinib in a Chinese patient population was comparable to previously reported global phase 3 trial results that included predominantly Caucasian patients with relapsed/refractory CLL,” the study authors wrote. “This is particularly important, as evidence has demonstrated notable differences in the frequency of common genetic mutations and chromosomal abnormalities between Asian and European patients with CLL.”

The phase 2 portion of the open-label study enrolled patients with relapsed/refractory CLL at 20 sites in China. Patients needed to be at least 18 years of age, have received at least 1 prior systemic regimen for CLL, and have an ECOG performance status of 2 or less. Those with significant cardiovascular disease or known central nervous system involvement of lymphoma/leukemia or leptomeningeal disease were excluded from the trial.

Eligible patients received oral acalabrutinib at a dose of 100 mg twice daily in 28-day cycles until disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

The primary end point was ORR assessed by BICR per iwCLL 2018 criteria. Secondary end points included investigator-assessed ORR and time to response, as well as DOR, progression-free survival (PFS), and time to next treatment (TTNT).

At baseline, the median age was 62 years (range, 33-77). Most patients were male (68.3%), had an ECOG performance status of at least 1 (96.7%), and had IGHV unmutated disease (51.7%). The median number of prior lines of therapy was 1 (range, 1-4).

Additional findings from the trial showed that the median PFS, OS, and TTNT were all NR. The 12- and 18-month PFS rates per BICR were 91.5% (95% CI, 80.9%-96.4%) and 78.8% (95% CI, 60.9%-89.2%), respectively. These respective OS rates were both 96.7% (95% CI, 87.3%-99.2%). Data from a subgroup analysis showed that the ORR was generally consistent across prespecified subgroups.

The median duration of treatment was 19.4 months (range, 0.6-28.2). In terms of safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 96.7% of patients, with 41.7% experiencing grade 3 or higher TEAEs. Serious TEAEs (15.0%), serious TEAEs related to treatment (13.3%), and TEAEs leading to death (1.7%) were also reported. TEAEs led to dose interruption, modification, or discontinuation at rates of 21.7%, 1.7%, and 3.3%, respectively.

The most common any-grade TEAEs included decreased neutrophil (40.0%), platelet (33.3%), and hemoglobin (23.3%) counts. Grade 3 or higher TEAEs included decreased neutrophil count (13.3%), upper respiratory tract infection (6.7%), and pneumonia (6.7%).

“This is the first study to evaluate the efficacy and safety of acalabrutinib for the treatment of relapsed/refractory CLL in a Chinese patient population,” study author wrote in their conclusion. “With a median time on study of 20.2 months, acalabrutinib demonstrated a high ORR with durable responses. Efficacy results were similar [with] trials of relapsed/refractory CLL in Caucasian populations.”

Reference

Yang S, Huang H, Zhou K, et al. Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: primary analysis from an open-label, multicenter phase 1/2 trial. Ann Hematol. 2025;104(1):701-712. doi:10.1007/s00277-024-05978-4