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.
The FDA included the following warning in their press announcement:
“The drug is being approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, but the company will be required to submit additional clinical information after approval to confirm the drug’s clinical benefit.”
References:
1. U.S. Food and Drug Administration. FDA approves Adcetris to treat two types of lymphoma. Web. August 22, 2011.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm268781.htm
2. Younes A et al, “Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas”, The New England Journal of Medicine 2010 Nov 4; 363: 1812-21. http://www.ncbi.nlm.nih.gov/pubmed/21047225
Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.
Reviewed August 24, 2011
by Michele Blacksberg R.N.
Edited by Jody Smith