CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients

CLL14 randomised 432 previously untreated patients with CLL and coexisting conditions (CIRS score above 6 or creatinine clearance under 70 mL/min) to 12 cycles of venetoclax plus obinutuzumab or chlorambucil plus obinutuzumab. The primary endpoint was investigator-assessed progression-free survival. At 24 months PFS was 88.2% versus 64.1% (hazard ratio 0.35), and undetectable MRD in peripheral blood three months after treatment ended was 75.5% versus 35.2%. Grade 3-4 neutropenia and infections were similar between arms. With six years of follow-up more than half of venetoclax-obinutuzumab patients remained progression-free against roughly a fifth on chemo-immunotherapy, though overall survival was not significantly different.