Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma

Introduction: New agents for managing B-cell non-Hodgkin lymphomas (NHLs) are needed, particularly for high-risk and relapsed or refractory patients. Antibody-drug conjugates (ADCs) provide targeted drug delivery to tumors with a broaden therapeutic index of cytotoxic agent, reducing their systemic toxicity while increasing intracellular concentrations. Polatuzumab vedotin, an anti-CD79b conjugated to the microtubule inhibitor monomethyl Auristatin E (MMAE) raises particular interest.

Areas covered: We discuss here polatuzumab vedotin development, challenges of designing a successful ADC, preclinical studies and recent trials, leading to FDA approval and the ongoing phase III POLARIX trial.

Expert opinion: Clinical data from early studies hold promises for polatuzumab vedotin in association with rituximab-bendamustine in relapsed or refractory (R/R) DLBCL and other combinations are investigated in this setting. In first line, with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP), promising results lead to develop the phase III POLARIX trial that may represent a new advance for untreated patients. If dosing and scheduling are adequately managed to avoid peripheral neuropathy risk, polatuzumab vedotin might become a key component of DLBCL therapeutic management. This antibody drug conjugate also offers new opportunities of combination with non-cytotoxic agents or immunological interventions that might reshape the treatment of DLBCL in the future.