Polatuzumab

Polatuzumab is a monoclonal antibody–drug conjugate (ADC) used in the treatment of B-cell non-Hodgkin lymphomas, most notably diffuse large B-cell lymphoma (DLBCL). It consists of a humanized anti-CD79b antibody linked to a cytotoxic agent, monomethyl auristatin E (MMAE), via a protease-cleavable valine–citrulline linker. The antibody targets CD79b, a component of the B-cell receptor complex, delivering MMAE to malignant B cells while aiming to limit exposure to non-target cells.

Mechanism of action involves binding to CD79b on the surface of B cells, followed by internalization and trafficking to lysosomes. The linker is cleaved inside the cell, releasing MMAE, which disrupts microtubule polymerization. This leads to cell cycle arrest and apoptosis of the B-cell cancer cells. The targeted delivery of MMAE helps to maximize anti-tumor activity while attempting to reduce systemic toxicity.

Clinical use and regulatory status have focused on diffuse large B-cell lymphoma in various treatment contexts. Polatuzumab vedotin is approved in combination regimens for relapsed or refractory DLBCL in adults, most commonly with rituximab and bendamustine, as part of a salvage therapy approach. It has also been studied in frontline settings; notably, a frontline trial evaluated a polatuzumab-containing regimen that replaces vincristine in a rituximab–cyclophosphamide–doxorubicin–prednisone backbone, with reported improvements in progression-free survival in newly diagnosed DLBCL in some regulatory jurisdictions.

Adverse effects commonly associated with polatuzumab-containing regimens include cytopenias (neutropenia, anemia, thrombocytopenia), infections, fatigue, nausea, diarrhea, and peripheral neuropathy. Serious adverse events can occur, and treatment requires careful monitoring of blood counts, organ function, and infectious risks.