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

8015 Background: Acala is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients (pts) with CLL including those with R/R CLL. The efficacy and safety of acala alone vs IdR or BR were shown in R/R CLL pts in a preplanned interim analysis of ASCEND; final results are reported herein. Methods: In this randomized, multicenter, phase 3, open-label study (NCT02970318), R/R CLL pts were randomized 1:1 to receive oral (PO) acala 100 mg BID or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or toxicity; R: 375 x1 then 500 mg/m2 intravenously [IV] for 8 total infusions) or BR (B: 70 mg/m2 IV and R: 375 x1 then 500 mg/m2 IV for 6 total cycles) until progression or toxicity. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed. Results: 310 pts (acala, 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 m, acala significantly prolonged INV-assessed PFS vs IdR/BR (median: not reached vs 16.8 m; hazard ratio: 0.27, P<0.0001); 18-m PFS rates were 82% for acala and 48% for IdR/BR. 18-m OS rate was 88% for both treatment regimens. ORR was 80% with acala vs 84% with IdR/BR (ORR + partial response with lymphocytosis: 92% vs 88%, respectively). Common adverse events (AEs) are listed in the Table. AEs led to drug discontinuation in 16% of acala, 56% of IdR, and 17% of BR pts. AEs of interest included atrial fibrillation (acala 6%, IdR/BR 3%), major hemorrhage (all grade; acala 3%, IdR/BR 3%), grade ≥3 infections (acala 20%, IdR/BR 25%), and second primary malignancies excluding non-melanoma skin cancer (acala 5%, IdR/BR 2%). Conclusions: Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acala compared with standard-of-care regimens in R/R CLL pts. Clinical trial information: NCT02970318 . [Table: see text]