Phase 1b/2 Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in Relapsed/Refractory B-Cell Lymphoma: Safety, Efficacy and Molecular Analysis

Background:Aggressive B-cell non-Hodgkin lymphoma (NHL) can be cured with chemoimmunotherapy; however, those who fail primary therapy and those with indolent NHL are rarely curable. Targeted agents can disrupt key survival pathways in NHL such as regulation of apoptosis (BCL2: venetoclax), B-cell receptor signaling (BTK: ibrutinib), and NF-κB survival pathways (IRF4/SPIB: lenalidomide). These agents are active as monotherapy but fail to induce deep responses and require continuous therapy. Also, genetically defined subtypes of NHL that best respond to these targeted agents are undefined. Synergistic cytotoxicity has been shown with these targeted therapies and corticosteroids in DLBCL cell lines. We hypothesized that combining agents that target multiple survival pathways will leverage efficacy and time-limited, cyclic dosing will limit toxicities.