Dr. Diehl Discusses Brentuximab Vedotin

Volker Diehl, MD, Professor of Medicine, Emeritus, University of Cologne, Germany, discusses the recently approved drug brentuximab vedotin (SGN-35), an antibody-drug conjugate that has been approved to treat anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma. It is marketed as Adcetris by Seattle Genetics, Inc.

Brentuximab vedotin builds on the CD30 tumor marker discovered 30 years ago in cell line L428. CD30 is present in ALCL and Hodgkin lymphoma. The naive monoclonal antibody anti-CD30 is ineffective by itself and requires the combination with another agent to be successful.

Diehl describes the chemists at Seattle Genetics as being very intelligent for adding a "bump" to the antibody in the form of monomethyl auristatin E (MMAE), a microtubule inhibitor. Once MMAE enters the CD30-expressing tumor it prevents mitosis within the cells, which causes targeted cell death.

The use of brentuximab vedotin in refractory and far advanced relapsing patients with Hodgkin's lymphoma resulted in an approximate complete remission of 35%. This drug is currently being used in combination with Adriamycin (doxorubicin), vinblastine, and dacarbazine (AVD) in the US.

In Germany a new regimen was constructed by modifying BEACOPP (Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone) in order to incorporate brentuximab vedotin. The modifications leave out procarbazine and long-term prednisone while adding brentuximab vedotin, dacarbazine, and dexamethasone.