mosunetuzumab + polatuzumab vedotin + rituximab

This is a combination therapy consisting of three monoclonal antibody-based agents—**mosunetuzumab**, **polatuzumab vedotin**, and **rituximab**—used primarily for the treatment of relapsed or refractory large B-cell lymphoma (LBCL), particularly in patients who are ineligible for stem cell transplantation. - **Mosunetuzumab** is a bispecific monoclonal antibody that binds both CD20 on B-cells and CD3 on T-cells, redirecting T-cells to eliminate malignant B-cells. - **Polatuzumab vedotin** is an antibody-drug conjugate targeting CD79b on B-cells and delivering the cytotoxic agent monomethyl auristatin E (MMAE), which disrupts microtubules and induces apoptosis. - **Rituximab** is a monoclonal antibody targeting CD20 on B-cells, leading to B-cell depletion via multiple immune-mediated mechanisms. Clinical evidence shows the dual regimen of mosunetuzumab plus polatuzumab vedotin is highly active in relapsed/refractory LBCL, improving progression-free survival with a manageable toxicity profile. The triplet combination with rituximab is mechanistically rational and under clinical investigation, but current published pivotal data are for the doublet (mosunetuzumab + polatuzumab vedotin). The primary mechanism combines T-cell activation (CD20/CD3 engagement), direct cytotoxicity (CD79b-directed ADC), and immune-mediated B-cell lysis (anti-CD20). Development is primarily led by Roche/Genentech, with potential for outpatient, fixed-duration administration.