Three-drug Combination 'Extremely Promising' As First-line Therapy For Multiple Myeloma

The three-pronged regimen of Velcade, lenalidomide (Revlimid) and dexamethasone -- referred to as Rev/Vel/Dex -- has achieved an overall response rate of 98 percent in 42 patients evaluated thus far in a Phase 1-2 trial, said Paul Richardson, MD, of Dana-Farber and the study's principal investigator. He added that 52 percent of the patients had high quality responses (very good partial response or better), with 30 percent achieving complete response to date.

"These may be some of the best response rates we've seen to date with up-front therapies, and although these are preliminary results, they are extremely promising," Richardson said. The patients were previously untreated when they received the Rev/Vel/Dex combination.

Velcade is a "smart" drug known as a proteasome inhibitor that blocks the myeloma cells' waste disposal system, creating an accumulation of toxic compounds that poison the cell. Revlimid is a chemical relative of thalidomide that affects several pathways in cancer cells, including immune mechanisms and blood vessel growth to tumors. Dexamethasone is a steroid hormone that counters inflammation and is used to treat hematologic malignancies such as myeloma. Studies leading to the trial of the three drugs in combination were carried out at Dana-Farber.

While these are the first results from trials of Rev/Vel/Dex given as initial, first-line therapy for the blood cancer, the combination has already been shown effective for multiple myeloma patients who had relapsed following successful treatment or who had not responded to standard therapies.

Richardson also reported at the ASH meeting preliminary data from a Dana-Farber led multicenter Phase 2 trial of the combination in relapsed or refractory myeloma. "These data confirm the favorable side effect profile," said Richardson, "and the response rate of 72 percent -- including complete, partial, and minor responses -- is very encouraging."

The responses, he added, appear to be holding up well, with a duration of more than one year for some patients to date. Both trials will continue to enroll patients, and final results are expected next year.