New Study Focuses on Precursor Conditions for Multiple Myeloma

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Stand Up To Cancer [announces a new] Dream Team focused on revolutionizing the treatment of multiple myeloma, which today is an incurable form of blood cancer of plasma cells. The team hopes that through early detection of precursor conditions, cancer can be intercepted before it turns into full-blown disease.


The SU2C Multiple Myeloma Dream Team will be led by Irene Ghobrial, MD, associate professor of medicine at Dana-Farber Cancer Institute (DFCI) in Boston and co-director of the Center for the Prevention of Progression of Blood Cancers at DFCI, with Ivan M. Borrello, MD, associate professor of oncology at Johns Hopkins University School of Medicine and director of the Cell Therapy and GMP Biologics Core at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, as co-leader.


Multiple Myeloma (MM) is, for now, an incurable cancer of the plasma cells. Almost all patients diagnosed with MM have had one of two precursor conditions, either monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM.) These conditions do not always progress to become cancer, but people who do get MM nearly always have warning signs – or precursor conditions –before their disease has caused damage to organs such as bone lesions, fractures and kidney failure. However, most patients are not diagnosed with these precursor conditions because there is no routine screening for them.


"We tell people with precursor conditions that we will 'watch and wait' until it turns into multiple myeloma, with multiple tumors that can potentially cause organ damage," Dr. Ghobrial said. "That's like telling people with breast cancer or colon cancer that we are not going to do anything until the cancer metastasizes throughout the body."

"We want to change that," she said.


Most patients are not diagnosed with these precursor conditions because there is no routine screening for them. By identifying these people before cancer develops, the Team can possibly develop therapies that prevent myeloma, making myeloma a cancer that can be prevented by early screening and interception.

MGUS is a very common condition that affects 3 percent of the general population aged 50 years or older. Risk increases with age. It is three times more common in African-Americans and presents at an even younger age in this population. Unlike expensive and controversial screening studies for other cancers, MGUS can be screened for by a simple blood test. However, this has not been the practice to date.


The SU2C Multiple Myeloma Dream Team revolves around a simple idea: to screen individuals who are at high risk of developing MGUS/SMM. By identifying them early, the Team can possibly develop therapies that prevent myeloma, making myeloma a cancer that can be prevented by early screening and interception.


The hypothesis of this proposal is that early detection of MGUS/SMM in a high-risk population, along with a good understanding of the molecular and immune factors that lead to disease progression, will lead to effective strategies that intercept disease progression and improve survival.


The Dream Team proposes to conduct a screening study of individuals over the age of 45, who are at a high risk for having MGUS or SMM, such as African-Americans and individuals who have a first-degree relative that has been diagnosed with a plasma cell disorder. This study will be called the PROMISE study. We will focus on these populations because they are two to three-fold more likely than others to have these precursor conditions.


The Team expects to screen 50,000 individuals to obtain 3,000 MGUS/SMM cases to intensively study and follow over time as a cohort. The Dream Team will study this cohort in an effort to define biological characteristics that will help to identify which patients will benefit from particular therapies. These biological characteristics include inherited mutations, acquired mutations, and immune factors. The Dream Team will also identify lifestyle and demographic factors that contribute to disease progression, such as obesity and race.


The Dream Team will use this information to develop new therapeutics that that can be used to prevent MM from progressing. These include novel technologies of nanoparticles for better imaging of early disease and the first personalized neoantigen vaccine study for the population of patients screened.


Together, these studies promise to change the landscape of myeloma diagnosis/screening and early prevention and interception of this disease. These studies will not only lead to better molecular markers that predict progression but also define therapeutic options that will make MM a preventable or possibly curable disease.

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