Multicenter phase 3 trial of ibrutinib plus venetoclax versus FCR for previously untreated CLL

The phase 3 UK NCRI FLAIR Study, at 96 centers in the UK, compared ibrutinib (I) plus venetoclax (V) with MRD-directed duration of treatment versus fludarabine-cyclophosphamide-rituximab (FCR) for previously untreated CLL. The study randomized 523 patients (71.3% male; median age 62 years; 40.9% Binet stage C) to I+V (n=260) or FCR (n=263). MRD (defined as <1 CLL cell in 10,000) was assessed at 12 months, and then 6-monthly. The primary end point was investigator-assessed progression-free survival. The figure shows that I+V was superior for the end points progression-free and overall survival. Serious adverse events were reported for 123 I+V patients and 129 FCR patients. The authors conclude that I+V with duration guided by MRD is a new gold standard for CLL treatment.