New Data at ASH 2015 from the Multiple Myeloma Research Foundation (MMRF) CoMMpass StudySM Show Significant Advances in the Understanding of Multiple Myeloma Genomics

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NORWALK, Conn.--(BUSINESS WIRE)-- The Multiple Myeloma Research Foundation (MMRF) is presenting today new data from the MMRF CoMMpass StudySM – the most comprehensive long-term genomic study ever conducted in myeloma and one that may significantly advance the understanding of multiple myeloma. The data provide significant insights into the genetics of multiple myeloma and the potential association to patient outcomes, as well as informing the development of more precision treatments for the disease.

Data from the latest interim analyses of the MMRF CoMMpass Study – part of the MMRF end-to-end system in precision medicine – are being presented at the American Society of Hematology (ASH) annual meeting in Orlando, Fla. The research, which reveals mutations that may trigger disease onset and progression and may be used to assess response to treatment, includes data about genetic differences among African Americans, as well as new data that uncover specific cellular pathways.

“These latest findings from the MMRF CoMMpass Study deepen our understanding of the genomics of multiple myeloma, allowing researchers and the medical community to better focus on the mechanisms behind this cancer and personalize care for patients,” said Walter M. Capone, President and Chief Executive Officer of the MMRF. “Securing this type of data from the MMRF CoMMpass Study is a crucial step towards finding a cure for multiple myeloma.”

MMRF CoMMpass Study Abstracts:

Identification of Initiating Trunk Mutations and Distinct Molecular Subtypes: An Interim Analysis of the MMRF CoMMpass Study

Abstract #722, Oral Presentation (Jonathan Keats, Translational Genomics Research Institute), , (), W224ABEF, Level 2

  • This is the first public presentation of the MMRF CoMMpass Study Interim Analysis 7 (IA7) cohort with 760 enrolled patients of whom 565 are molecularly characterized. It evaluated genetic mutations and how they affect progression-free survival and overall survival among patients being treated with proteasome inhibitors, immunomodulatory (IMiD) agents or a combination of both. Although the median follow-up time for the entire cohort is short and data is still maturing, subjects on proteasome plus IMiD based triplet combinations are currently showing a trend toward PFS and OS benefit compared to those receiving doublet combinations with each agent alone. Furthermore, this current analysis has identified likely tumor initiating mutations and new subtypes of myeloma, which are associated with distinct molecular events and clinical outcomes.

In-Depth Molecular Profiling of Multiple Myeloma in African Americans

Abstract #2973, Poster Presentation (Zarko Manojlovic, Translational Genomics Research Institute), , (Session: ), Hall A, Level 2

  • This analysis of the MMRF CoMMpass Study, which includes a total of 93 African Americans (AA) and 377 European Americans (EA) with whole genome data from IA7, evaluated genetic differences between the two populations. African Americans are more than twice as likely as white Americans to be diagnosed with multiple myeloma (the reason for this increase in risk remains unknown). The MMRF CoMMpass Study is unique in that it included an unprecedented study population of 17% African Americans, compared to an average of 5% seen in other studies. Even though overall there was no statistical difference in non-silent mutation burden between the two populations, noticeable trends were observed in the TP53 mutation occurrence (1% in AA and 9% in EA) and higher mutation frequencies in tumors from African Americans in genes implicated in epigenetic regulatory mechanisms. Also, a lower frequency of IgH translocations such as t(4;14) was observed in tumors from AA patients (10%) compared to tumors from EA patients (37%), a result supporting our previously reported difference for this alteration between these two groups.

Investigation of Mechanisms of Response in Multiple Myeloma Via Bayesian Causal Inference: An Early Analysis of the CoMMpass Study Data

Abstract #1794, Poster Presentation (Fred Gruber, GNS Healthcare), , (Session: ), Hall A, Level 2

  • In this analysis of the MMRF CoMMpass IA7 dataset focusing on 452 cases with full clinical and molecular data, the MMRF and the Emory University School of Medicine, along with several leading bioinformatics groups, including GNS Healthcare, the Translational Genomics Research Institute and Instat, worked together to reverse-engineer the molecular pathways that most likely affect treatment outcomes and to assess their significance in treatment response. Key drivers of clinical outcomes fell into broad categories 1) known response drivers, 2) drivers in known pathways, and 3) potential novel biology, or false positives; all three groups were broadly represented among top results. Of interest, subjects who underwent stem cell transplant showed a trend toward better outcome in this analysis.

“The importance of these observations as well as others involving potential new genes and pathways will be followed closely in future CoMMpass interim analyses to validate their significance,” said Sagar Lonial, MD, Professor and Executive Vice Chair, Department of Hematology and Medical Oncology, Chief Medical Officer, Winship Cancer Institute, Emory University and Global Lead Investigator for the MMRF CoMMpass Study. “We expect current and future results from the MMRF CoMMpass Study will promote the discovery of further drivers of clinical outcomes to benefit patients.”

About the MMRF CoMMpass StudySM

The MMRF CoMMpass Study is a longitudinal study of patients with newly diagnosed active multiple myeloma. The goal is to map the genomic profile of each patient to clinical outcomes to develop a more complete understanding of patient responses to treatments. A cornerstone of the MMRF’s Personalized Medicine Initiative, the study will collect and analyze tissue samples, clinical data and genetic information from 1,000 newly diagnosed multiple myeloma patients for at least eight years.

The study is designed to show which treatments are used most often as first and subsequent lines of therapy, and to correlate this information with critical therapeutic response criteria including best responses achieved, overall survival, time to disease progression and quality of life measures. Each patient enrolled in the study is required to receive an approved proteasome inhibitor, immunomodulatory drug or both.



The MMRF CoMMpass Study opened in July of 2011 and now includes 1,000 patients from more than 100 sites in the United States, Canada and European Union. Data from the MMRF CoMMpass Study is made available to researchers via the MMRF’s Researcher Gateway (http://research.themmrf.org), an online, open-access portal designed to make key genomic and clinical data available for additional study. The MMRF CoMMpass Study is being supported through a public-private partnership of patient donors and industry partners, including Takeda Oncology, Amgen, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc. and Janssen Diagnostics. Additional collaborating research partners include the Translational Genomics Research Institute, Van Andel Research Institute and GNS Healthcare.

Please visit www.themmrf.org/research-partners/the-commpass-study to learn more about the study.

About Multiple Myeloma

Multiple myeloma (MM) is a cancer of the plasma cell. It is the second most common blood cancer.1 According to the National Cancer Institute, an estimated 26,850 adults in the United States will be diagnosed with MM in 2015 and an estimated 11,240 people are predicted to die from the disease. The five-year survival rate for MM is approximately 47%, versus 31% in 1999.2

About the Multiple Myeloma Research Foundation

The Multiple Myeloma Research Foundation (MMRF) was established in 1998 as a 501(c) (3) non-profit organization by twin sisters Karen Andrews and Kathy Giusti, soon after Kathy’s diagnosis with multiple myeloma. The mission of the MMRF is to relentlessly pursue innovative means that accelerate the development of next-generation multiple myeloma treatments to extend the lives of patients and lead to a cure. As the world’s number-one private funder of multiple myeloma research, the MMRF has raised more than $300 million since its inception and directs nearly 90% of its total budget to research and related programming. As a result, the MMRF has been awarded Charity Navigator’s coveted four-star rating for 11 consecutive years, the highest designation for outstanding fiscal responsibility and exceptional efficiency.

About the Multiple Myeloma Research Consortium

The Multiple Myeloma Research Consortium (MMRC) is a 509 (a) 3 non-profit organization that integrates leading academic institutions to accelerate drug development in multiple myeloma. It is led from MMRC offices in Norwalk, Conn., and comprises 22 member institutions: Dana-Farber Cancer Institute, Massachusetts General Hospital Cancer Center Home, Beth Israel Deaconess, Brigham and Women's Hospital, Mayo Clinic (Jacksonville, Rochester and Scottsdale), Baylor Charles A. Sammons Cancer Center at Dallas, Barbara Ann Karmanos Cancer Institute, City of Hope, Emory University’s Winship Cancer Institute, Levine Cancer Institute, The John Theurer Cancer Center at Hackensack University Medical Center, Mount Sinai School of Medicine, Ohio State University, Sarah Cannon Research Institute, University Health Network (Princess Margaret Hospital), University of California, San Francisco, University of Chicago, University of Michigan, Virginia Cancer Specialists and Washington University in St. Louis.

The MMRC is the only consortium in multiple myeloma to join academic institutions through membership agreements, customized IT systems, and an integrated tissue bank. For more information, please visit www.themmrc.org.

References

1. American Cancer Society. What are the risk factors for multiple myeloma? Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-risk-factors. Accessed .

2. National Cancer Institute, National Institute of Health, U.S. Dept. of Health and Human Services. SEER Stat Fact Sheets: Myeloma. Available at http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed .

Media
Multiple Myeloma Research Foundation
Sharon Saias, 203-652-0211
Vice President, Marketing & Communications
saiass@themmrf.org

Source: Multiple Myeloma Research Foundation

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