Drug Combination Proves Effective Against Myeloma In Phase I Trial

The trial -- the first and largest reported to date to test the drugs bortezomib (Velcade) and lenalidomide (Revlimid) in combination -- involved 38 myeloma patients whose disease had recurred after previous treatment and was progressing despite other therapies.

Participants were divided into groups that received successively higher doses of the drugs. Some also received dexamethasone, a standard myeloma medication which adds to the effects of both bortezomib and lenalidomide, if the combination alone no longer controlled their disease.

The researchers, led by Paul Richardson, MD, and Ken Anderson, MD, of Dana-Farber, found that 58 percent of 36 evaluable patients responded to lenalidomide and bortezomib, including six percent who had complete remission, despite being heavily pre-treated and, in most cases, having received both classes of drug before. The median length of remission was six months, with some patients having disease control for up to two and a half years. The combined therapy also produced only mild fatigue or peripheral neuropathy (nerve damage signaled by tingling or numbness), researchers found. Patients who received dexamethasone because their disease continued to progress on the drug combination found the additional drug tolerable, and it produced a response or disease stabilization in about three quarters of them.

"It is remarkable to see the combination prove both tolerable and engender such durable responses in resistant disease," Richardson says. "We are hopeful that this combination will prove to be a key therapeutic backbone in improving outcomes for our patients, both early and later in their course."

Both Velcade and Revlimid are relatively recent additions to doctors' arsenal against multiple myeloma. Velcade thwarts myeloma cells by interfering with their ability to break down and dispose of certain proteins. Revlimid also attacks the tumor cells directly and disrupts their interactions with surrounding tissue in the bone marrow.

The trial was based on preclinical work that found Revlimid increases myeloma cells' vulnerability to Velcade and dexamethasone, which suggested that patients might benefit from a combination of them. The encouraging results of the Phase I study have prompted investigators to begin Phase II trials of the combined therapy in patients with newly diagnosed myeloma and in hard-to-treat, relapsed cases. Phase III trials are also planned.

Richardson and his colleagues will lead an oral presentation on the findings on Monday, Dec. 11, at 11:30 a.m. ET in the Chapin Theater (Level III) (Abstract 405).

Co-authors of the study include researchers at Dana-Farber, St. Vincent's Comprehensive Cancer Center, New York; Beth Israel Deaconess Medical Center, Boston; H. Lee Moffitt Cancer Center, Tampa, Fla.; Celgene, Inc., of Summit, N.J.; and Millennium Pharmaceuticals, Inc., of Cambridge, Mass.

The research was funded by Millennium, Celgene, and the Jerome Lipper Multiple Myeloma Center at Dana-Farber.