Brentuximab Vedotin (SGN-35), an antibody-drug conjugate for the treatment of CD30-positive malignancies

Introduction: CD30-positive hematological malignancies are potentially curable with frontline combination chemotherapy regimens; however, those patients who relapse or are refractory to initial therapies have less favorable prognosis. Areas covered: Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the potent antimicrotubule drug monomethylauristatin E connected by a protease-cleavable linker. Treatment with single-agent brentuximab vedotin resulted in unprecedented objective response rates and complete response rates of 75 and 34%, respectively, in relapsed or refractory Hodgkin lymphoma, and of 86 and 57%, respectively, in relapsed or refractory systemic anaplastic large-cell lymphoma patients. Peripheral sensory neuropathy and neutropenia were observed with brentuximab vedotin but were generally grade 1 and 2 in severity and manageable. In August 2011, brentuximab vedotin was approved in the US for the treatment of Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in ASCT-ineligible candidates, and for the treatment of systemic anaplastic large-cell lymphoma after failure of at least one prior multiagent chemotherapy regimen. Expert opinion: These data support an expanded development program for brentuximab vedotin in multiple CD30-positive indications.