CLL-091: Acalabrutinib Versus Idelalisib Plus Rituximab (IdR) or Bendamustine Plus Rituximab (BR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): ASCEND Final Results

Abstract

Context Acalabrutinib is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients with CLL. The efficacy and safety of acalabrutinib versus IdR/BR were previously reported in R/R CLL patients in a preplanned interim analysis of ASCEND ( NCT02970318 ). Objective To report final results from the ASCEND study. Design Randomized (1:1), phase 3, open-label study. Setting Multicenter clinical trial. Patients Patients with R/R CLL. Interventions Oral acalabrutinib 100 mg twice daily (BID) or investigator's choice of IdR (Id: 150 mg orally BID until progression/toxicity; R: 375 × 1 then 500 mg/m2 intravenously for 8 total infusions) or BR (B: 70 mg/m2 intravenously; R: 375 × 1 then 500 mg/m2 intravenously for 6 total cycles) until progression/toxicity. Main outcome measures Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety. Results 310 patients (acalabrutinib, n=155; IdR, n=119; BR, n=36) were enrolled (median age: 67 y; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 months, acalabrutinib significantly prolonged investigator-assessed PFS vs IdR/BR (median: not reached vs 16.8 months; hazard ratio: 0.27, P Conclusion Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acalabrutinib compared with standard-of-care regimens in R/R CLL patients.