Acalabrutinib With Obinutuzumab (Ob) In Treatment-Naive (Tn) And Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (Cll): Three-Year Follow-Up.

7500 Background: Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor. This Phase 1b/2 trial evaluated acalabrutinib with the CD20 antibody Ob in TN and R/R CLL. Methods: Patient (pts) with TN and R/R (≥1 prior therapy) CLL were eligible. In 28-day cycles, acalabrutinib was given at 100 mg BID or 200 mg QD PO (n=15; all switched to 100 mg BID) until progressive disease (PD); Ob was given in standard fashion for 6 cycles starting with Cycle 2. The primary endpoints were overall response rate (ORR) and safety. Minimal residual disease (MRD) was assessed using flow cytometry (sensitivity 10 -4 ). Results: 19 TN and 26 R/R pts were treated; median age of all pts was 61 y (range 42-76). Pt characteristics, disposition, efficacy and MRD are in the Table. Common adverse events (AEs; any grade) were upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%) and dizziness (47%). Common Gr 3/4 AEs were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight and cellulitis (9% each). There were 2 (4%) Gr 3 bleeding events (hematuria, muscle hemorrhage) and 1 (2%) Gr 3 atrial fibrillation event. Conclusions: Acalabrutinib plus Ob was well tolerated and yielded high response rates that were durable and deepened over time in TN and R/R CLL patients. Clinical trial information: NCT02296918. [Table: see text]