|A major breakthrough in multiple myeloma treatment is reported in this week's New England Journal of Medicine (NEJM). Sagar Lonial, MD, assistant professor of hematology and oncology at Emory's Winship Cancer Institute, is one of the authors of the paper, "Bortezomib or High Dose Dexamethasone for Relapsed Multiple Myeloma." It outlines a phase III clinical trial, which was conducted at Emory and other sites around the world and clearly shows the benefits of treatment with bortezomib.
Last year, multiple myeloma, which is a plasma cell malignancy, was diagnosed in more than 15,000 people in the United States and accounts for approximately 11,000 deaths each year. Although high dose chemotherapy and bone marrow transplant have shown some success in treatment, median survival from myeloma remains 3 to 5 years and virtually all patients eventually die from the disease.
"This study has set the stage for the next major revolution in myeloma therapy," says Dr. Lonial. "Bortezomib is one of a new class of drugs known as proteosome inhibitors that have been effective against several tumors. This is now clearly an important advance in the battle against hematologic cancers."
Proteosome inhibitors are designed to specifically inhibit the proteasome, which is an enzyme complex in the cell that is responsible for breaking down a variety of proteins, including many that regulate cell division.
They are not like traditional chemotherapy drugs. This drug works at the molecular level. It will interrupt the mechanism that the myeloma cells use to reproduce themselves. "If you reduce the number of cancer cells, you reduce the malignancy," says Dr. Lonial.
"The proteosome inhibitor prevents the accelerating cycle of malignant cell growth by inhibiting specific aspects of myeloma cells that give them a survival advantage over surrounding cells," he says.
What makes this new drug exciting to investigators like Dr. Lonial and their patients is the fact that it only targets the myeloma cells and has less impact on normal cells. "The normal cells appear to resume their routine functions once the effect of the drug dissipates, but for the malignant cells, the inhibition is often significant enough to result in cell death," says Dr. Lonial.
"More work needs to be done with bortezumib and other proteasome inhibititors," says Dr. Lonial, "however, we are clearly seeing development of a new class of drugs that is providing much needed impact with patients with relapsed or refractory myeloma."
Phase III clinical trials were conducted at 60 sites in the United States, Canada and Europe by Millenium Pharmaceuticals, based in Cambridge, Mass.