Preliminary Safety and Efficacy from a Multicenter, Investigator-Initiated Phase II Study in Untreated TP53 Mutant Mantle Cell Lymphoma with Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen)

Background: TP53 mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with chemoimmunotherapy (Eskelund Blood 2017) and there is no standard frontline treatment for this high-risk patient population. The combination of Bruton's Tyrosine Kinase (BTK) inhibition and the BCL2 inhibition have been shown to be synergistic and active in relapsed, refractory MCL, including in patients with TP53 mutation (Tam NEJM 2018). Obinutuzumab, ibrutinib, and venetoclax has been shown to be well tolerated and associated with high response rates in relapsed and untreated MCL patients (Le Gouill Blood 2021). We hypothesize that treatment with zanubrutinib (B; BGB-3111; BTK inhibitor), obinutuzumab (O; CD20 antibody), and venetoclax (Ven; BCL2 inhibitor) (BOVen) will be well tolerated and efficacious in untreated TP53 mutant MCL.