CLL-186 interim results from ASSURE: a phase 3b safety study of acalabrutinib in patients with chronic lymphocytic leukemia.

Abstract

Context: Acalabrutinib is a second-generation Bruton tyrosine kinase inhibitor approved for treatment-naive (TN) or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Objective(s): To report interim safety results from ASSURE (NCT04008706) evaluating acalabrutinib monotherapy in patients with CLL in a real-world clinical practice setting. Design(s): Multicenter, open-label, single-arm, phase 3b trial. Patient(s): Patients aged >=18 years with CLL requiring therapy and ECOG performance status <=2 enrolled into 1 of 3 cohorts (TN, R/R, or ibrutinib intolerant [IbrI]). Intervention(s): Oral acalabrutinib 100 mg twice daily for 48 cycles of 28 days each (beyond if still benefitting from drug) or until disease progression or discontinuation for any reason. Main Outcome Measure(s): Frequency of all treatment-emergent adverse events (TEAEs). Result(s): A total of 552 patients received treatment (TN, n=310; R/R, n=202; IbrI, n=40). Median age overall was 69.5 years (20% had del(17p)/TP53m, 68% had uIGHV). Median number of prior therapy lines was 1 and 2 in R/R and IbrI cohorts, respectively. At data cutoff (June 15, 2023), 64% remained on treatment. Median (range) duration of exposure was 32.1 (0.2-43.6), 32.3 (0.6-41.5), and 20.5 (0.7-33.0) months in the TN, R/R, and IbrI cohorts, respectively. Estimated proportion of patients remaining on treatment at 30 months (95% CI) by Kaplan-Meier was 71% (66-76), 62% (55-69), and 45% (27-62) in the TN, R/R, and IbrI cohorts, respectively. Grade >=3 TEAEs were reported in 57% of patients overall (TN, 54%; R/R, 63%; IbrI, 45%), most commonly COVID-19 (13%), pneumonia (7%), anemia (6%), and COVID-19 pneumonia (5%). TEAEs led to treatment discontinuation in 19% of patients. Incidences of atrial fibrillation/flutter, hypertension, and major hemorrhage were low. TEAEs with outcome of death were reported in 56 patients, most occurring in patients with confirmed/suspected COVID-19 (n=41). TEAE deaths in patients without confirmed/suspected COVID-19 (n=15) included infections/infestations (n=4) and neoplasms (malignant/unspecified; n=4). Conclusion(s): In this interim analysis of ASSURE, the safety profile of acalabrutinib in patients with CLL in a real-world clinical setting was consistent with previous clinical studies, except for COVID-19 TEAEs, which were commonly observed as study enrollment spanned the COVID-19 pandemic. No new safety signals were reported.Copyright © 2024 Elsevier Inc.