Acalabrutinib in TN and R/R CLL/SLL: Long-term phase II study results

Long-term results from the phase I/II ACE‑CL‑001 trial (NCT02029443), evaluating acalabrutinib monotherapy in patients with treatment-naïve (TN; n = 99) or relapsed/refractory (R/R; n = 134) chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL), were published in Blood Advances by Furman et al. The primary endpoint was safety, assessed through adverse events (AEs), laboratory testing, and vital signs. Secondary endpoints include overall response rate (ORR), duration of response (DoR), and progression-free survival (PFS). 

Key data: Overall, 99.7% of patients experienced ≥1 treatment-emergent AE (TEAE) of any grade and 71.1% of patients experienced Grade ≥3 AEs. The most common Grade ≥3 TEAEs were hypertension (12.1%), weight increase (8.1%), pneumonia (8.1%), neutropenia (8.1%), diarrhea (6.1%), syncope (6.1%), and headache (5.1%) in the TN cohort and neutropenia (15.7%), pneumonia (15.7%), hypertension (11.2%), anemia (7.5%), and syncope (6.0%) in the R/R cohort. Serious AEs (SAEs) occurred in 49.5% of patients in the TN cohort and in 63.4% of patients in the R/R cohort. The ORRs were 97.0% and 94.8% in the TN and R/R cohorts, respectively. The median PFS was not reached (NR) in the TN cohort and 66.1 months in the R/R cohort. The median EFS was 79.1 months in the TN cohort and 53.8 months in the R/R cohort.

Key learning: Long-term acalabrutinib monotherapy demonstrated durable efficacy and a manageable safety profile with no new safety signals in TN and R/R CLL/SLL.