Brentuximab vedotin: an anti-CD30 antibody-drug conjugate

The pharmacology, pharmacokinetics, clinical efficacy, and safety and tolerability of brentuximab vedotin are reviewed.

Brentuximab vedotin is a potent antibody-drug conjugate composed of the monoclonal antibody cAC10, which targets the CD30 antigen on Hodgkin lymphoma and systemic anaplastic large-cell lymphoma (sALCL) cells; a highly stable valine-citrulline linker; and a potent chemotherapeutic agent monomethyl auristatin E, which inhibits microtubule polymerization. Brentuximab is indicated for patients with relapsed Hodgkin lymphoma after autologous stem-cell transplantation (ASCT), for patients who are not candidates for ASCT who have not responded to at least two multiagent chemotherapy regimens, and for patients with ALCL who have not responded to at least one multiagent chemotherapy regimen. In a Phase II, single-group, multicenter study, brentuximab produced an overall response rate of 75% in relapsed or refractory Hodgkin lymphoma. In another Phase II study, brentuximab demonstrated clinical benefit in sALCL, with 86% of patients achieving a response and 57% of patients achieving complete remission. Adverse events most commonly reported included nausea, fatigue, diarrhea, neutropenia, and peripheral sensory neuropathy. A Phase III study is currently ongoing in patients at high risk for residual Hodgkin lymphoma after ASCT.

Brentuximab vedotin, a novel antibody-drug conjugate combining a cytotoxic agent with a selective monoclonal antibody, is a therapeutic option for patients with relapsed or refractory Hodgkin lymphoma and sALCL. Phase I and II studies have shown brentuximab to have a manageable toxicity profile.