Multinational phase 3 trial of first-line venetoclax combinations in chronic lymphocytic leukemia in fit patients

Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (aCLL) have been lacking. A multinational phase 3 trial randomized fit aCLL patients without TP53 aberrations 1:1:1:1 to receive six cycles of standard chemoimmunotherapy or twelve cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. For the endpoints undetectable minimal residual disease at 15 months and progression-free survival, venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy. Venetoclax-rituximab was not superior to chemoimmunotherapy. Grade 3 or 4 infections were more frequent with chemoimmunotherapy and venetoclax-obinutuzumab-ibrutinib than with the other two combinations (quick take video summary).