Multiple myeloma clinical trial shows distinct survival benefit with lower dose of steroids

Results of Eastern Cooperative Oncology Group Phase III clinical trial E4A03, for multiple myeloma, showing significantly better overall survival with lenalidomide plus low-dose dexamethasone therapy compared to lenalidomide plus high-dose dexamethasone, were reported today by S. Vincent Rajkumar, M.D. at the American Society of Hematology's annual meeting.

Currently lenalidomide and high-dose dexamethasone, referred to as Rev/Dex, is used as second-line treatment for myeloma. This same treatment has been used off-label (not currently approved by the U.S. Food and Drug Administration (FDA) for this particular use) by physicians for their newly-diagnosed patients, with overall response rates and one-year survival rates in the 90 percent range.

“The standard treatment for myeloma usually includes high doses of steroids such as dexamethasone. In this study we were hoping to find that a lower dose of steroids would be just as effective,” says Dr. Rajkumar, Mayo Clinic Cancer Center hematologist and lead investigator of the study. “We were surprised to find that the regimen with high-dose steroids actually was decreasing survival, besides contributing to increased side effects.”

The study compared combination treatment of oral medications lenalidomide (a novel chemotherapeutic agent) and either high- or low-dose dexamethasone (a potent steroid effective against myeloma) in 445 patients with newly diagnosed myeloma. Lenalidomide plus high-dose dexamethasone had an 18-month survival rate of 80 percent. The comparative therapy using low-dose dexamethasone showed a significantly higher 91 percent overall survival rate at 18 months, with much less toxicity.

“The lower survival rates with the high-dose dexamethasone can be attributed to disease progression as well as treatment-related toxicities,” says Dr. Rajkumar. “This is a major advance in the treatment of this cancer, and also gives researchers a new direction to explore -- that more is not necessarily better.”

All patients on the high-dose dexamethasone arm of the clinical trial were moved to the low-dose arm in April 2007, following an early closure announcement.