Fixed-Duration CLL Regimens Match Continuous Ibrutinib on PFS in Head-to-Head Trial

Overview

• Researchers randomized 909 newly diagnosed adults with CLL to continuous ibrutinib, 12 cycles of venetoclax with obinutuzumab, or venetoclax after three cycles of ibrutinib.
• At a median 34-month follow-up, progression-free survival was 81.0% with continuous ibrutinib, 81.1% with venetoclax–obinutuzumab, and 79.4% with ibrutinib–venetoclax, meeting non-inferiority.
• Complete responses were 51.5% with venetoclax–obinutuzumab and 46.2% with ibrutinib–venetoclax versus 8.3% with continuous ibrutinib, and undetectable MRD occurred in 73% and 62% of patients in the fixed-duration arms but in none on ibrutinib alone.
• Overall adverse-event rates were similar, with more cardiovascular events tied to prolonged ibrutinib exposure and more severe infections plus shorter PFS in aggressive disease linked to obinutuzumab.
• The investigator-initiated study was published in NEJM and will be presented at the ASH Plenary Session, with ongoing follow-up and biomarker studies planned to refine patient selection.