Velcade Prolongs Survival in Relapsed Myeloma

Abstract

June 17, 2005Trial results support earlier use of new myeloma drugResearchers say Velcade warrants testing as first-line therapy

Final results of a large Phase III trial in relapsed multiple myeloma patients show that bortezomib, or Velcade, clearly outperformed a standard drug therapy for patients with relapsed myeloma and now warrants further testing as initial therapy for the blood disease, say researchers from Dana-Farber Cancer Institute.

The largest trial of its kind, the APEX study compared Velcade against high-dose dexamethasone in 669 patients who had been previously treated with other drugs but had relapsed.

An article in the June 16 issue of the New England Journal of Medicine reports that Velcade caused a partial or total response in 38 percent of patients, compared with 18 percent for dexamethasone. The Velcade patients went an average of 6.2 months before the disease progressed again; the time to progression was 3.5 months in patients taking dexamethasone. Four out of five, or 80 percent, of Velcade patients were alive one year later, a significant improvement over the 66 percent of patients on high dose dexamethasone.

"This drug has shown itself to be superior to high-dose dexamethasone in time-to-progression, response rate and survival, with a side-effect profile that is manageable," said Paul Richardson, MD, of Dana-Farber, who led the multicenter trial. "These results provide confirmation that bortezomib should be used at first relapse, and they provide a strong rationale for its use as an upfront therapy."

This year, nearly 16,000 new cases of multiple myeloma will be diagnosed in the United States and 11,300 people likely will die from the disease. In multiple myeloma, cancerous plasma cells form abnormal proteins and damage the bone marrow, bone, and other vital organs. Standard treatment with combination chemotherapy and stem-cell transplants achieves responses, but myeloma remains incurable.

The use of both drugs in the study was associated with serious adverse events, and nearly one-third of patients discontinued one or the other drug because of side effects. Richardson, who is also an assistant professor at Harvard Medical School, said that bortezomib has an importantly different side effect profile compared to high-dose dexamethasone. The researchers have developed strategies to reduce the drug's adverse effects, such as peripheral neuropathy, but , he adds that bortezomib-treated patients do not experience some of the very challenging problems associated with high dose dexamethasone, including glucose intolerance, weight gain and mood swings.

Bortezomib is the first of a new type of cancer drug designed to attack cancer cells by blocking the proteasome, a mechanism by which cells eliminate abnormal proteins. The drug, sold as Velcade by Millennium Pharmaceuticals, Inc. of Cambridge, Mass., was extensively studied preclinically for the treatment of myeloma by Teru Hideshima MD PhD, and other investigators at Dana-Farber's Jerome Lipper Multiple Myeloma Center, under the directorship of Kenneth Anderson MD. Richardson and Anderson then helped design and lead the first pivotal Phase II clinical trial completed in 2001, as well as this subsequent confirmatory study.

Millennium won initial accelerated Food and Drug Administration approval of Velcade for relapsed and refractory myeloma in 2003, well before this Phase III trial was completed in 2004. In March of this year, the FDA granted full approval of Velcade for myeloma patients who have received at least one prior therapy.

Richardson is first author of the NEJM report and Anderson is senior author. Other authors are from medical centers in the United States, Canada, Israel and Europe, and from Millennium Pharmaceuticals.

The study was supported in part by funding from Millennium Pharmaceuticals.

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.