Multicenter phase 3 trial of first-line ibrutinib-rituximab versus fludarabine-cyclophosphamide-rituximab for chronic lymphocytic leukemia

The approval of BTK inhibitors in patients with previously untreated CLL was based on trials which compared ibrutinib with alkylating agents in patients considered unfit for fludarabine, cyclophosphamide, and rituximab, the most effective chemoimmunotherapy in CLL. The multicenter phase 3 trial FLAIR in the UK compared frontline ibrutinib-rituximab versus fludarabine, cyclophosphamide, and rituximab in CLL. Interim analysis of the trial found that ibrutinib-rituximab significantly improved progression-free survival but did not improve overall survival. A small number of sudden unexplained or cardiac deaths in the ibrutinib-rituximab group were observed largely among patients with existin hypertension or history of cardiac disorder.