A novel combination of an anti-CD20 antibody obinatuzumab (G) and the Bcl-2 inhibitor venetoclax (Ven) provides a new solution for unfit CLL patients. This combination resulted in durable remissions on the CLL14 trial regardless of IGHV mutational status, therefore overcoming unmutated VH status as an indicator of poor prognosis. HR, hazard ratio; IGHVmut, IGHV mutated; IGHVunm, IGHV unmutated.