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SCOR in High Risk Plasma Cell Dyscrasias

Robert Orlowski

Robert Orlowski

PhD, MD

The University of Texas MD Anderson Cancer Center

Project Term: October 1, 2017 - September 30, 2022

Dr. Orlowski assembled an experienced, collaborative group of researchers who work in a multidisciplinary manner on projects focusing on basic, translational, and clinical aspects of smoldering multiple myeloma (SMM) and multiple myeloma (MM). Both high risk SMM and MM represent important and urgent unmet medical needs for the development of novel, more effective therapies.

Lay Abstract

Multiple myeloma (MM) is the second most commonly diagnosed blood-related tumor. The incidence of MM increases with age. Therefore, with an aging population, it is expected that new cases in the US will grow by almost 60% from 2010 to 2030, ranking it third among all cancers in the rate of increase during this time. Myeloma remains incurable in the vast majority of patients, but many new therapeutic options have become available in the last 10-15 years. Patients with myeloma precursor states, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), continue to progress to symptomatic myeloma. This is especially true for MGUS and SMM that have higher-risk features, through mechanisms that we do not fully understand. Frustratingly, no therapies are approved for use in patients with myeloma precursor states. Watchful waiting without treatment remains the standard of care, and we still cannot predict for sure which patients will progress and which will not. Moreover, though survival has indeed improved overall, this has been largely in patients with standard-risk disease. In contrast, those with high-risk symptomatic myeloma subtypes continue to have an average survival from diagnosis of only three years, and less than one year if they have relapsed and/or treatment-refractory disease.

Those with high-risk MGUS and SMM, as well as high-risk symptomatic myeloma, represent a population with a truly unmet and urgent medical need for the development of novel, targeted approaches to improve their outcomes. A better understanding of the molecular and immunologic mechanisms that contribute to the aggressive behavior of high-risk myeloma will uncover weaknesses in these cancers that can be targeted with new therapies to improve patient outcomes.

There are two overall goals of our SCOR. The first goal is to study patients with MGUS and SMM using advanced tools to understand the molecular features of their disease so we can better predict who is at greatest risk of progression. From this information, we will develop an immunotherapy-based approach, which can be personalized to each patient, that will delay and prevent progression to full blown myeloma, thereby avoiding the need for chemotherapy. The second goal is to develop and study unique models of some of the most common high-risk myeloma subtypes that will allow identification and testing of new therapies that will improve outcomes in these patients. To accomplish these goals, we have assembled an experienced group of myeloma researchers at MD Anderson who will work closely together on four projects focusing on high-risk MGUS, SMM, and MM. Successful completion of these studies will support our goals of rapidly developing and moving to the clinic new “designer” treatments that could be personalized to the underlying myeloma and associated immune components of patients with high-risk disease, thereby improving their outcomes.

Program
Specialized Center of Research Program
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