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.

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Dr. Volker Diehl from the University of Cologne Discusses Brentuximab Vedotin 

Dr. Diehl Discusses Brentuximab Vedotin 

Volker Diehl, MD, Professor of Medicine, Emeritus, University of Cologne, Germany, explains the differences between the staging of Hodgkin Lymphoma in the US and Europe.

Western countries such as the US and Canada use 2 stages for Hodgkin's Lymphoma: early and advanced. In Europe 3 stages exist: early, intermediate, and advanced. Because of these differences in staging practice roughly 30-35% of what would be the European intermediate stage is bundled into the advanced section in the US. The lack of an intermediate level may result in the over treating of patients.

Diehl explains that a patient diagnosed with a stage I bulk, with B symptoms, Hodgkin Lymphoma would receive 6 courses over 6 months of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) in the US, but would only receive 2 doses over the span of 2 1/2 months in Europe.

The extra courses received in the US opens patients up to more adverse reactions. The side effects of adriamycin are cardiotoxicity and bleomycin can result in lung toxicities. Diehl questions whether the advantages of the extra chemotherapy outweigh the risks involved with the ABVD treatment.

Dr. Volker Diehl from the University of Cologne, Germany, Compares US and EU Hodgkin Lymphoma Staging

Dr. Diehl Compares US and EU Hodgkin Lymphoma Staging

Volker Diehl, MD, Professor of Medicine, Emeritus, University of Cologne, Germany, explains that Hodgkin's lymphoma is unique because the microenvironment contains a minority of tumors cells and an abundance of reactive cells.

This disease demonstrates an intelligent interaction between the microenvironment and the tumor cells. When treating Hodgkin's lymphoma is it necessary to kill all cells including the inert tumor cells and the not yet well-defined clonogenic cells that interact with the microenvironment.

Dr. Volker Diehl from the University of Cologne, Germany on the Unique Nature of Hodgkin's Lymphoma

Volker Diehl, MD

Articles

Dr. Diehl Discusses Brentuximab Vedotin

Dr. Diehl Compares US and EU Hodgkin Lymphoma Staging

Dr. Diehl on the Unique Nature of Hodgkin's Lymphoma