Study
| Phase 3, multicenter, open-label, randomized trial (AMPLIFY) |
| 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% |
| Major hemorrhage: uncommon |
| Tumor lysis syndrome: 0.3% vs. 0.4% vs. 3.1% |
| Covid-19 related deaths: 10 vs. 25 vs. 21 |
N Engl J Med. Published February 5, 2025
http://doi.org/10.1056/NEJMoa2409804
Reviewed by Ulas D. Bayraktar, MD on Feb 7, 2025
