Bortezomib and Lenalidomide effective in Myeloma

Abstract

Two "new generation" drugs for the bone marrow cancer multiple myeloma may work even bettertogether than they do individually, according to the results of a multicenter Phase I clinical trial to be presented by Dana-Farber Cancer Institute scientists at the annual meeting of the American Society of Hematology in Orlando, Fla.

The trial the first and largest reported to date to test the drugs bortezomib (Velcade®) andlenalidomide (Revlimid®) in combination involved 38 myeloma patients whose disease had recurredafter 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 58percent of 36 evaluable patients responded to lenalidomide and bortezomib, including sixpercent who had complete remission, despite being heavily pre-treated and, in most cases, havingreceived both classes of drug before. The median length of remission was six months, with somepatients having disease control for up to two and a half years. The combined therapy also producedonly mild fatigue or peripheral neuropathy (nerve damage signaled by tingling or numbness), researchers found. Patients who received dexamethasone because their disease continued toprogress 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 durableresponses in resistant disease," Richardson says. "We are hopeful that this combination will proveto be a key therapeutic backbone in improving outcomes for our patients, both early and laterin their course."

Both Velcade and Revlimid are relatively recent additions to doctors' arsenal against multiplemyeloma. Velcade thwarts myeloma cells by interfering with their ability to break down anddispose 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.

Co-authors of the study include researchers at Dana-Farber, St. Vincent's Comprehensive CancerCenter, 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.

Dana-Farber Cancer Institute (www.dana-farber.org) 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.

For more information, contact: Teresa Herbert; Rob Levy; 617.632.4090.