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Industry has made significant inroads over the years against multiple myeloma - Millennium Pharmaceuticals Inc.'s Velcade, approved in May 2003, comes to mind - but academia also has chalked up important gains against the rare, deadly blood cancer.

And that has not gone unnoticed by the National Cancer Institute, which has awarded a $17.9 million grant to the Little Rock, Ark.-based Myeloma Institute for Research and Therapy, part of the Arkansas Cancer Research Center at the University of Arkansas for Medical Sciences (UAMS).

It's the second renewal of a grant relationship that began in 1989, said Joshua Epstein, director of laboratory affairs at the institute, and the work is "ongoing until we cure the disease."

Having recently reached a milestone of 5,000 stem cell transplants - more than any other facility in the world - the institute plans to move into new facilities and expand its work. The five-year NCI grant funds an ongoing program titled "Growth Control of Multiple Myeloma."

Remission rates for patients at the institute over the last decade have improved from less than 5 percent for those given standard chemotherapy to more than 50 percent for patients who get both chemotherapy and stem cell transplants, which involve collecting peripheral stem cells before chemotherapy and giving them back afterward.

Autologous stem cell transplants are one way to treat multiple myeloma, along with radiation therapy and chemotherapy. Drug therapies include Cambridge, Mass.-based Millennium's Velcade (bortezomib); Thalomid (thalidomide) from Celgene Corp., of Warren, N.J.; and Emeryville, Calif.-based Chiron Corp.'s Aredia (pamidronate disodium, which targets osteolytic bone lesions, in conjunction with standard anti-myeloma chemo).

The proteasome inhibitor Velcade was widely hailed, and "is revolutionary in the sense that it elicits responses in patients who haven't responded to anything else," Epstein said. "It's not a magic bullet, but it's remarkable."

Could Velcade, which sold $35 million in the second quarter, become the preferred mode of treatment? Possibly, but in Epstein's view "there is no favorite [now]. Whatever works on a patient is the favorite."

Coming down the pike in the late stages of research are such approaches as Seattle-based NeoRx Corp.'s Skeletal Targeted Radiotherapy and Genasense (oblimersen sodium) from Genta Inc., of Berkeley Heights, N.J.

Genasense in another indication - melanoma, to be used with dacarbazine - drew a negative vote from an FDA advisory panel in May, but Genta is going ahead with the myeloma bid. Celgene's Revlimid, a derivative of Thalomid, also fizzled against melanoma but still is in a Phase III program for multiple myeloma. (See BioWorld Today, April 29, 2004.)

Funds from the NCI are earmarked for four ongoing research projects, as well as four supportive cores at the institute, which is the first facility in the world created specifically to study and treat multiple myeloma. The average survival rate of a myeloma patient once was two to three years upon diagnosis, but the UAMS institute has pushed the number to seven years and beyond.

The four research projects are titled, "Strategies for Cure in Newly Diagnosed Multiple Myeloma," "Developmental Therapeutics," "Elucidating the Role of the Microenvironment in Multiple Myeloma Through Global Gene Expression Profiling," and "Targeting Heparan Sulfate for Myeloma Therapy."

None has been pegged to get more money than another, Epstein said.

"It doesn't work this way," he said. "They're all interrelated," with scientists from each helping the others. "Together they can form a nucleus that will be much more effective than individual investigations."

The helpful interdependence of project scientists is echoed malignantly in multiple myeloma itself, Epstein told BioWorld Today.

"These cells thrive in an environment of other cells, supposedly normal tissues," he said. "We know from long experience and from new data that one has to address what we consider the microenvironment. There's good evidence to indicate that Velcade and other agents not only affect the tumor cells, but the cells in the microenvironment, the supporting cells, as well."

Multiple myeloma research is "very difficult," Epstein said. "The biggest problem has been that the cells don't like to grow in culture, and there didn't used to be any decent models to study them in." That situation changed over the years. Cultured cells achieved by the researchers "don't increase in numbers," he said, "but they have a nice interaction with some cells in the microenvironment" - and studying that interaction will be a key.

Velcade has been celebrated as a proteasome inhibitor and "it may be doing this, but apparently it's also doing other things," Epstein said. "Even though we had a reason to use it and we thought we knew why, it may not be exactly the mechanism or the only mechanism by which it works."

The genomics aspect of multiple myeloma research has been a challenge, Epstein said.

Scientists now are using fluorescent in situ hybridization (FISH) assays to some benefit, although "its clinical relevance is still being tested. The other [method] is gene-expression profiling," he said. "This appears to be very nicely related to translocations that activate or silence genes, and it's relatively new."

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