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Adcetris Targets CD30 Cells in Hodgkin's Lymphoma

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On August 19, 2011, the FDA approved the first new drug since 1977 to treat Hodgkin's lymphoma. Adcetris (brentuximab vedotin) is also approved for a rare type of lymphoma called systemic anaplastic large cell lymphoma.

This drug takes a novel approach to treating lymphoma, according to a paper published in the New England Journal of Medicine by Dr. Anas Younes of the University of Texas M.D. Anderson Cancer Center and colleagues at other universities. Seattle Genetics, of Bothell, Washington developed the drug and paid for the research.

Conventional chemotherapy kills rapidly dividing cells in general, leading to high toxicity. Adcetris is one of the new generation of targeted therapy drugs that is designed to attack a specific feature of the cells of a particular cancer type. The target is the CD30 cell membrane protein which is expressed on the surface of certain types of lymphoma cells, including Hodgkin's Reed-Sternberg cells, anaplastic large-cell lymphoma cells, embryonal carcinoma cells, and other cells found in select types of non-Hodgkin lymphoma.

It is also expressed on a small fraction of normal B and T cells and eosinophils. Because of the large difference in CD30 levels between normal and lymphoma cells, Younes explained, “deletion of CD30-expressing cells could represent a novel and selective treatment strategy”.

Younes described Adcetris as an antibody-drug conjugate. The antibody part is an anti-CD30 monoclonal antibody that was not very effective in treating lymphoma by itself. The drug part is monomethyl auristatin E (MMAE), which is an antitubulin agent that blocks cell division. Adcetris uses the antibody to deliver the drug to the appropriate lymphoma cells.

Conventional therapy fails to produce remission in approximately 15 to 30 percent of patients with Hodgkin's lymphoma, Younes reported. For these patients, the next step is autologous hematopoietic stem-cell transplantation, which is effective for about half. When this treatment also fails, the overall survival rate is only 32 percent at 5 years. Adcetris is now an option for patients who have not responded to conventional chemotherapy or stem-cell treatment.

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