Lenalidomide plus low-dose dexamethasone produces significantly better overall survival for patients with multiple myeloma than lenalidomide plus high-dose dexamethasone, according to a presentation at the annual meeting of the American Society of Hematology.

The findings from the Eastern Cooperative Oncology Group Phase III clinical trial E4A03 for multiple myeloma were reported by S. Vincent Rajkumar, MD.

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 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," said 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 and either high- or low-dose dexamethasone 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 steroid 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," said 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.