UAMS Myeloma Institute Continues to Develop Newer, More Effective Therapies on Arkansas Medical News Inc.

UAMS Myeloma Institute Continues to Develop Newer, More Effective Therapies

By: BECKY GILLETTE

Dr. Bart Barlogie

Progress results from novel research and its applications

Multiple myeloma is one of the most difficult kinds of cancer to treat effectively. In fact, when Bart Barlogie, MD, PhD, founded the University of Arkansas Center for Medical Sciences (UAMS) Myeloma Institute for Research and Therapy in 1989, there was debate about whether or not it was possible to cure myeloma at all.

Today the Myeloma Institute in Arkansas is considered the world leader in the field of research and treatment for this disease.

“The past 21 years have been a time of significant progress in the care of patients with multiple myeloma,” said Barlogie, director of the UAMS Myeloma Institute.

“Our myeloma program in Arkansas has developed innovations that have taken us directly from research to the treatment of patients who represent all age groups, nationalities, and levels of disease. The tremendous strides we have made in changing the outcome for myeloma patients stem from novel research and its applications.”

People come from around the country and the world to be treated in Little Rock; patients include people from 50 countries. About 65 percent of the patients—which now total more than 9,000 – come from outside of the state. About 8,000 bone marrow transplants have been performed at the center, and more than 350 peer-reviewed publications have been published by clinical and research staff.

Barlogie said some of the treatment innovations developed at the center include:

Combination chemotherapy using VAD (Vincristine, Adriamycin, Dexamethasone)
Tandem bone marrow transplants with increased remission rates
Bone marrow transplants for patients over the age of 70
Introduction of thalidomide as a treatment for myeloma
Cytogenetic research to identify chromosomal prognostic factors
Genetic chip analysis to identify high and low risk disease

“The Myeloma Institute has treated large numbers of patients on its own clinical protocols, thus assuring that new knowledge is incorporated into front line therapies,” Barlogie said. “We have an extensive comprehensive data base that includes information from 70,000 cytogenetic tests, MRI exams on more than 5,000 patients, and PET-CT scans on more than 1,000 patients. We have annotated salvage trial data and overall outcomes that can be used to match newly referred patients with historical patients and thus aid in treatment decisions.”

Myeloma Institute Director of Development Therapeutics Saad Zafar Usmani, MD, said survival rates for patients treated through the Myeloma Institute has improved so much that there is no longer a debate about whether there is a cure for this cancer.

“We have learned a great deal from the clinical investigations over the past two decades,” Usmani said. “That is the reason for success and the improved overall survival rates. Our goal is to continue our mission, and part of that is evaluating new drugs which will do well with the combination chemotherapy we have already come to know that works. Our eventual goal is to come up with the best, individualized combination of drugs that will cure each myeloma patient based on features unique to their disease. That is a big statement, but that has always been the goal of this program. We have certainly progressed in that direction over the past two decades. And the results are significant and there for all to see.”

A patient with low-risk multiple myeloma, which is determined by genetic testing, who is treated at the Myeloma Institute can expect to survive more than 10 years.

The National Cancer Institute reports that for newly diagnosed multiple myeloma patients in the U.S. between 1995 and 2001, 34 percent lived at least five years. The Myeloma Institute had nearly double that amount of success with 57 percent of newly diagnosed patients during the same time period living five years or more. That kind of success is the reason why the Myeloma Institute now treats more multiple myeloma patients than any other cancer center in the world.

The focus is on attacking myeloma on all fronts from the very beginning, applying a carefully crafted combination of available agents and treatment principles.

The Myeloma Institute now has two new trials in addition to the first known as Total Therapy 1, 2, 3a, and 3b.

“Starting in 1989 with Total Therapy 1 (TT1), we have designed and conducted a series of clinical trials that have each built on lessons learned from the previous trials,” Usmani said. “Thus, Total Therapies 1, 2, 3a and 3b have seen advances in patient survival and complete response resulting from incorporating new agents and adjusting therapies to support the stem-cell transplants.”

The transition from TT1 to TT2 introduced the drug Thalidomide before and after transplantation and TT3a added Bortezomib to the TT therapy backbone. The transition to TT3b included addition of Lenalidomide and Bortezomib as maintenance therapy.

Usmani said they are now working on trials for TT4 and TT5.

“New therapies and drugs are emerging that are very exciting,” Usmani said. “There are special new drugs including Carfilzomib, a tetrapeptide epoxyketone and a selective proteasome inhibitor, and Pomalidomide, a chemotherapy drug that is classified as an immunomodulatory agent and an antiangiogenic agent. These two drugs are emerging as very important against myeloma and we are incorporating these new drugs into our current medical trials. We are also exploring other novel therapies, such as natural killer cell therapy, other newer drugs such as proteasome inhibitors and Histone Deacetylase (HDAC) inhibitors and monoclonals antibodies. There are a multitude of new things being brought into clinical trials so our patients can benefit. “

Patients seen at the clinic include not just newly diagnosed patients, but people who have been treated elsewhere and run out of treatment options.

“Then they come to us,” Usmani said. “We don’t turn anyone away. We study their disease from a biology perspective and try to find a good strategy for them.

We are enrolling patients on three TT trials. With each of these successive trials we had newer, more effective drugs coming down the pike. That is what makes our program so unique.”

TT 4 and 5 are the first-ever clinical trials in the world enrolling patients based on how the disease is defined, by the expressions of the genes from the cancer cells. TT3 patients had special gene expression profiling studies on the myeloma cells which has allowed the Institute to develop a predictive model to distinguish patients who had low risk of disease relapse versus higher risk of disease relapse. The proportion of patients at low risk was 80-85 percent, with 15-20 percent at high risk for relapse.

“So the TT4 program focuses on low-risk patients, and TT5 is for high-risk patients,” Usmani said. “The goal of TT5 for high-risk patients is to see if we can find a different way to treat our high-risk patients so they don’t relapse early. We do see success with our early results.”

Whether patients are treated inside or outside of a clinical trial, they receive the same high quality, team approach to care.

“That is what patients seem to fully appreciate,” Usmani said. “Research is a big part of our practice here. But at the end of the day, it is all about the patient.”