The internationally known multiple myeloma program at the University of Arkansas for Medical Sciences will receive $19.5 million over five years to continue work that has already developed new treatments for this cancer of plasma cells, a type of white blood cell present in the bone marrow.



In 2004, Bart Barlogie, M.D., Ph.D., director of the UAMS Myeloma Institute for Research and Therapy (MIRT), was awarded $17.9 million from the from the National Cancer Institute (NCI) to fund an ongoing comprehensive research program, entitled “Growth Control of Multiple Myeloma.” That grant was distributed over five years, concluding in June.



The $19.5 million NCI grant is the fourth five-year renewal of continuous funding from the NCI, which supports much of the ongoing research at the Myeloma Institute, a part of the UAMS Winthrop P. Rockefeller Cancer Institute. Barlogie’s work has led to a median survival rate of more than eight years today for Myeloma Institute patients, compared to a 34 percent five-year survival rate for multiple myeloma patients, as documented by the NCI between 1995-2001.



Myeloma Institute scientists have analyzed the genetic and cellular mechanisms of multiple myeloma, leading to new treatments for patients who come to UAMS from every state and more than 50 countries. With a genetic analysis tool developed at UAMS, a patient’s disease can now be identified as a more aggressive (high-risk) or less aggressive (low-risk) form of multiple myeloma.



Clinical trials under way are among the first for multiple myeloma or any other cancer to involve risk-specific treatment plans based on the genetic makeup of the tumor.



“Thanks to the basic science, clinical research and patient care efforts funded by this grant over the years, the landscape for myeloma outcomes has changed drastically,” said Barlogie, a professor in the UAMS College of Medicine.



The Myeloma Institute, the only center in the world devoted exclusively to research and clinical care related to multiple myeloma and related disorders, will mark its 20th anniversary at UAMS this year. Founded by Barlogie, the UAMS multiple myeloma program has seen more than 9,000 patients from every state in the United States and more than 50 foreign countries.



The latest trials, Total Therapy 4 for low-risk disease and Total Therapy 5 for high-risk disease, build on the success of earlier applications of the Total Therapy approach. Twenty-one percent of the 231 patients enrolled in UAMS’ initial multiple myeloma clinical trial, known as Total Therapy 1, are still alive beyond 10 years, with some alive at 19 years. About 55 percent of those enrolled in Total Therapy 2, started in 1998, are still alive. Of almost 480 patients enrolled in Total Therapy 3, initiated in 2003, 78 percent are alive; 83 percent of those with low-risk multiple myeloma are still alive after four years, including 85 percent in complete remission with no signs of multiple myeloma.



Of 95 patients enrolled in Total Therapy 4 starting in July 2008, 90 are alive. All 12 patients enrolled in Total Therapy 5, which began in October 2008, are still alive.



“This grant enables us to focus all efforts toward the common goal of controlling and defeating multiple myeloma,” Barlogie said.



The projects covered in the NCI grant renewal and the principal investigators include:



· Project 1: Strategies for Cure in Newly Diagnosed Multiple Myeloma – Barlogie is the principal investigator;

· Project 2: Developmental Therapeutics – principal investigator Frits van Rhee, M.D., Ph.D., professor of medicine in the UAMS College of Medicine and director of clinical research at the Myeloma Institute;

· Project 3: Tumor Cell-Microenvironment Interactions in the Molecular Pathogenesis of Multiple Myeloma – principal investigator John Shaughnessy, Ph.D., professor of medicine and biostatistics in the UAMS College of Medicine and director of the Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics at the Myeloma Institute; and

· Project 4: Targeting the Microenvironment for Myeloma Growth Control – principal investigator Shmuel Yaccoby, Ph.D., associate professor of medicine in the UAMS College of Medicine



The grant also funds several shared research areas, or cores, that support the funded projects. The research cores and their directors include:



· Research Core A: Administration, biostatistics and research coordination – Barlogie and co-director John Crowley, Ph.D., president and chief executive officer of Cancer Research and Biostatistics and director of the Statistical Center of the Southwest Oncology Group at the Hutchinson Cancer Research Center in Seattle;

· Research Core B: Cell Analysis and Specimen Banking – Joshua Epstein, D.Sc., a professor in the UAMS College of Medicine;

· Research Core C: Genomics and Proteomics – Shaughnessy;

· Research Core D: SCID-hu and In-vivo Modeling –Yaccoby; and

· Research Core E: Experimental Cellular Pathology – William Bellamy, Pharm.D., Ph.D.



In addition to the grant renewal, Myeloma Institute researchers also received other NCI grants that support the common research purpose:



· Elias Anaissie, M.D., a professor of medicine in the UAMS College of Medicine and director of supportive care at the Myeloma Institute, is studying variation in treatment side effects at the gene level;

· Van Rhee is investigating how innate immune cells can control or be made to control myeloma; and

· Epstein and Yaccoby are looking at how the interaction between myeloma cells with the bone marrow environment can be exploited to control myeloma growth.



UAMS treats more than 2,250 patients with multiple myeloma annually at the Myeloma Institute – more myeloma patients than are treated at any other facility in the country.