Previously untreated CLL without del(17p) or TP53 mutation
Acalabrutinib–venetoclax vs. acalabrutinib–venetoclax–obinutuzumab vs. chemoimmunotherapy (FCR or BR)
Efficacy
36-mo PFS: 76.5% vs. 83.1% vs. 66.5% (acalabrutinib–venetoclax vs. acalabrutinib–venetoclax–obinutuzumab vs. chemoimmunotherapy) (p=0.004 for acalabrutinib–venetoclax vs. chemoimmunotherapy; p<0.001 for acalabrutinib–venetoclax–obinutuzumab vs. chemoimmunotherapy)
ORR: 92.8% vs. 92.7% vs. 75.2%
36-mo OS: 94.1% vs. 87.7% vs. 85.9% (HR: 0.33 [0.18–0.56]; p<0.001 for acalabrutinib–venetoclax vs. chemoimmunotherapy)
Undetectable MRD at key time points: 26.8% vs. 66.4% vs. 51.0% (favoring acalabrutinib–venetoclax–obinutuzumab; p<0.001)
Safety
Any grade AEs: 95% vs. 96% vs. 91% (acalabrutinib–venetoclax vs. acalabrutinib–venetoclax–obinutuzumab vs. chemoimmunotherapy)
Grade ≥3 AEs:
32.3% vs. 46.1% vs., 43.2% (neutropenia)
Infections (grade ≥3): 12.4% vs. 23.6% vs. 10% (higher in acalabrutinib–venetoclax–obinutuzumab group)
Cardiac events: 9.3% vs. 12.0% vs. 3.5%
Atrial fibrillation/flutter: 0.7% vs. 2.1% vs. 0.8%
