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New myeloma drug shows promise in early testing

Targeted antibody well-tolerated; researchers encouraged by response

added 6/7/10

Ann Arbor - A drug designed to target cancerous plasma cells appears promising in treating multiple myeloma, a type of blood cancer.

A multi-center study looked at the drug elotuzumab, an antibody which is designed to target CS1, a protein on the surface of malignant plasma cells. The antibody has the potential to attach to malignant plasma cells and eliminates them by an immune mechanism. The early stage trial combined elotuzumab with bortezomib, or Velcade, one of the novel chemotherapies approved to treat multiple myeloma, a cancer that arises in the plasma cells.

"Elotuzumab was found to work in synergy with bortezomib in a pre-clinical model, which served as the basis for this clinic trial. The regimen was well-tolerated, and many patients stayed on it for a long time," says Andrzej Jakubowiak, M.D., Ph.D., director of the Multiple Myeloma Program at the University of Michigan Comprehensive Cancer Center. Jakubowiak presented results of the study at the American Society of Clinical Oncology annual meeting.

The study looked at 28 patients with multiple myeloma that had relapsed or become unresponsive to treatment. Overall, 48% responded to the elotuzumab and bortezomib combination and patients' cancer progressed after an average 9.45 months. These numbers are better than in previous studies of patients with less advanced disease treated with bortezomib alone in which 38 percent responded to the treatment and cancer progressed after an average of 6.22 months.

"The study was not designed to evaluate statistical superiority of the combination of elotuzumab and Velcade, but it does appear to support our preclinical evidence that these two drugs work together," Jakubowiak says.

The researchers will next consider a study to compare the combination of elotuzumab and bortezomib against standard therapy to see if the combination achieves better results.

Methodology:
28 people with multiple myeloma that had returned or was unresponsive to treatment were given four cycles of elotuzumab and bortezomib (Velcade). Elotuzumab was given twice in a three-week cycle, with increasing doses each time; and a standard dose of bortezomib was given four times during the cycle. Participants with stable disease after the four cycles continued treatment until their cancer progressed. Study participants had all previously received one to three other therapies before being enrolled in this study.

Multiple myeloma statistics:
20,580 Americans will be diagnosed with multiple myeloma this year and 10,580 will die from the disease, according to the American Cancer Society.

Additional authors:
Don M. Benson, Ohio State University; William Bensinger, Fred Hutchinson Cancer Research Center; David Siegel, Hackensack University Medical Center; Todd Zimmerman, University of Chicago; Ann Mohrbacher, University of Southern California; Paul Richardson, Dana-Farber Cancer Institute; Daniel Afar, Facet Biotech Inc.; Anil Singhal, Facet Biotech Inc.; Kenneth Anderson, Dana-Farber Cancer Institute.

Funding:
Facet Biotech and Bristol-Myers Squibb Company.

Disclosure:
Jakubowiak served as a consultant with honoraria for Millennium Pharmaceuticals, Celgene Corporation, Centocor Ortho Biotech, Bristol-Myers Squibb Company, and Exelixis, Inc.

Reference:
American Society of Clinical Oncology Annual Meeting, June 4-8, 2010, Chicago, Abstract No. 8003.

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Written by Nicole Fawcett

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