The Myeloma Institute is at the forefront of research. With a dedicated faculty conducting clinical as well as basic science research, we are at the cutting edge of scientific breakthroughs. Our patients benefit from the rapid transmission of laboratory findings to daily care in the clinical setting.
The Myeloma Institute has received continuous P01 grant funding from the National Cancer Institute for the Project Program “Growth Control of Multiple Myeloma” since 1993 for 20 consecutive years of uninterrupted funding. The objective of the P01 research is to improve growth control of multiple myeloma by dissecting and exploiting the molecular and biological consequences of the multiple myeloma – microenvironment interaction.
A hallmark of the Myeloma Institute for Research and Therapy is a program of clinical trials that challenge the traditional body of thought on disease treatment in order to improve outcomes. The physicians work in tandem with myeloma scientists to bring the “bench of research to the bedside of the patient” and back again to optimize diagnosis and treatments. Patients have access to the newest, cutting-edge therapies through enrollment onto physician investigator initiated clinical trials as part of a world-class clinical research program. The Myeloma Institute also partners with SWOG (formerly the Southwest Oncology Group) on collaborative, multi-center clinical trials, and also participates in pharmaceutical industry trials in order to give patients access to some of the latest pharmaceutical advances.
Our Total Therapy (TT) approach to treatment of multiple myeloma lies at the core of successful patient outcomes at the Myeloma Institute. The focus is on attacking myeloma on all fronts from the very beginning, applying a carefully crafted combination of available agents and treatment principles.
Starting in 1989 with Total Therapy 1, we have designed and conducted a series of clinical trials that have each built on lessons learned from the previous trials. Thus, Total Therapies 2 and 3 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 more intensive therapy before transplantation, as well as chemotherapy after transplantation, and TT2b also added thalidomide to the regimen. The transition to TT3 included thalidomide and added bortezomib.
By closely monitoring patients’ responses to each trial and conducting detailed analyses of individual patient’s disease characteristics, we have designed a progression of clinical trials that have shown steady improvements in patient outcomes.
To learn more about clinical trials, please visit the National Cancer Institute.
Click to view the current clinical trials actively enrolling patients at the Myeloma Institute.
The UAMS Myeloma Institute is the only facility in the world that routinely offers gene array analysis for newly referred patients and utilizes this information for patient management and planning of therapy. The Myeloma Institute performs multiple gene arrays on patients enrolled on investigator-initiated clinical trials.
Based on a study of more than 500 newly diagnosed patients treated at the Myeloma Institute for multiple myeloma, MIRT researchers found that the expression of just 17 genes (out of the 25,000 genes in the human body) revealed which form of myeloma a patient had. The expression level of those 17 genes serves as a powerful predictor of response to therapy.
This enables doctors to more accurately predict which patients will not respond to standard therapy and thereby spare patients from undergoing treatments that will not be effective. The discovery is also important to the development of new treatments that specifically target the 17 genes.
Complete findings are reported in plenary paper published in Blood.
Blood, 15 March 2007, Vol. 109, No. 6, pp. 2276-2284
A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1
John D. Shaughnessy Jr1,Fenghuang Zhan1,Bart E. Burington2,Yongsheng Huang1,Simona Colla1,Ichiro Hanamura1,James P. Stewart1,Bob Kordsmeier1,Christopher Randolph1,David R. Williams1,Yan Xiao1,Hongwei Xu1,Joshua Epstein1,Elias Anaissie1,Somashekar G. Krishna1,Michele Cottler-Fox1,Klaus Hollmig1,Abid Mohiuddin1,Mauricio Pineda-Roman1,Guido Tricot1,Frits van Rhee1,Jeffrey Sawyer1,Yazan Alsayed1,Ronald Walker1,Maurizio Zangari1,John Crowley2, andBart Barlogie1
Summary of Abstract
To molecularly define high-risk disease, researchers performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma.
Seventy genes were found to be linked to early disease-related death. Importantly, most up-regulated genes mapped to chromosome 1q, and down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up-regulated to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free survival, and overall survival. Shaughnessy’s data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions.
A central hypothesis of the work presented in this paper was that expression extremes of a subset of genes correlating with survival might be representative of the effects of DNA copy changes in myeloma disease progression. Shaughnessy and colleagues were thus able to identify a set of 70 genes, the expression levels of which permitted the identification of a small cohort of 13% to 14% of patients at high risk for early disease-related death.
The marked increase in the frequency of high-risk designation from 13% at diagnosis to 76% at relapse provides molecular evidence of disease evolution that influences postrelapse outcome. With further refinement of the model, Shaughnessy expects to develop tools for quantitative risk assessment during the entire course of therapeutic management.
The findings may also shed important light on the underlying molecular mechanisms that drive disease progression. This has the potential to translate into clinical applications that slow down or prevent disease progression.
Through multivariate discriminant analyses, Shaughnessy found that of the original 70 genes, 17 probe sets could be used to detect high-risk myeloma. Assessment of the expression levels of these genes may provide a simple and powerful molecular-based prognostic test that would eliminate the need for testing many of the standard variables currently in use with limited prognostic implications. If these gene signatures are unique to myeloma tumor cells, such a test may be useful after treatment to assess minimal residual disease, possibly using peripheral blood as a sample source.
Blood, 15 March 2007, Vol. 109, No. 6, pp. 2276-2284 A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1
The goal of this MRD project, led by Sarah Johnson, PhD, is to detect and enumerate by multiparameter flow cytometry residual tumor cells in patients with myeloma following high dose therapy, and to characterize these cells using highly sensitive molecular techniques. Hypothesizing that these cells are resistant to therapy and represent the cells responsible for eventual relapses, we expect that characterization of these cells will allow us to detect potential relapses much earlier than traditional methods and to incorporate therapeutic interventions designed specifically to target these cells.
Myelodysplastic Syndrome (MDS)
Myelodysplastic syndrome is a disease in which the bone marrow does not make enough healthy blood cells. In a healthy person, the bone marrow makes blood stem cells that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. Lymphoid stem cells become a white blood cell and myeloid stem cells become either red blood cells, platelets or white blood cells.
In a patient with a myelodysplastic syndrome, the blood stem cells do not become healthy red blood cells, white blood cells, or platelets. The immature blood cells (blasts) do not work the way they should and either die in the bone marrow or soon after they go into the blood, leaving less room for healthy white blood cells and greater risk of infection, anemia, or easy bleeding. Age and past treatment with chemotherapy or radiation therapy affect the risk of a myelodysplastic syndrome.
For this research, Joshua Epstein, PhD is focused on developing a predictive model for patients at risk of developing MDS as a result of extensive myeloma therapy.
Gene Expression Profiling (GEP)
Researchers at the Myeloma Institute use state-of-the-art gene array analysis to characterize molecular features of myeloma. They can apply this knowledge to more accurately predict which patients will benefit the most from specific therapies.
This GEP project led by Christoph Heuck, MD, involves the analysis of prospectively collected clinical data as well as tissue specimens from the approximately 10,000 patients treated at the Myeloma Institute since 1989. While GEP has been applied to a portion of specimens using modern high-throughput techniques, numerous samples collected prior to the introduction of GEP technology have not been processed. The project involves processing the untouched bone marrow aspirate and biopsy samples using GEP. Analysis of clinical data and tissue specimens will yield a more in-depth understanding of the biology of myeloma cells and their microenvironment.
The GEP data is being biostatistically integrated with clinical data in order to gain insight about factors that predict response to treatment as well as treatment targets based on pathogenesis.