BMS-986458 + glofitamab + obinutuzumab

This is a combination therapy consisting of BMS-986458, glofitamab, and obinutuzumab, currently under investigation for the treatment of relapsed or refractory non-Hodgkin lymphoma (NHL), particularly diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). - **BMS-986458** is an orally bioavailable, highly selective bifunctional cereblon (CRBN)-dependent ligand-directed degrader (aka protein degrader/PROTAC) that selectively induces degradation of B-cell lymphoma 6 (BCL6), a key oncogenic transcription factor frequently overexpressed in NHL[2][3][5]. By targeting BCL6, BMS-986458 drives anti-tumor effects, promotes cell-cycle arrest, and modulates immune microenvironments, and uniquely upregulates CD20 surface expression, potentially enhancing the activity of anti-CD20 agents[2][3]. - **Glofitamab** is a bispecific monoclonal antibody targeting CD20 on B cells and CD3 on T cells, recruiting T cells to eliminate B cells. - **Obinutuzumab** is a glycoengineered type II humanized anti-CD20 monoclonal antibody that induces B-cell lysis via antibody-dependent cellular cytotoxicity and direct cell death. This combination, used in emerging clinical protocols, aims to maximize anti-tumor efficacy by combining direct BCL6 degradation, immune system modulation, and strong B-cell targeting through two mechanisms (bispecific T-cell engagement and direct anti-CD20 activity)[2][3][5].