Multiple myeloma (MM) is a devastating hematologic malignancy that affects over 20,000 new patients every year in the USA. It typically responds well to treatment with DNA alkylators, glucocorticoids, proteasome inhibitors, and the IMiD class of Immunomodulator (thalidomide, lenalidomide and pomalidomide). Unfortunately, over time the disease becomes resistant to these drugs and patients relapse and die. We have identified 4 key areas of research that promise to translate into rapid clinical gains for the treatment of patients. 1) Develop dramatically new strategies to treat MM using next-generation approaches such as oncolytic virotherapy; 2) Given the success of IMiDs, study novel classes of immunomodulators with anti-MM activity, starting with SMAC mimetic compounds; 3) Determine the clinical significance of the most frequent mutation in MM, structural rearrangements of the MYC locus, and the effects of targeting MYC in patients with MM; 4) Explore clonal evolution in MM, including its contribution to drug resistance. To tackle these issues we have assembled a dedicated team of basic science and clinical investigators from all three Mayo Clinic sites, representing the largest MM program in the world. The projects are augmented by the strong collaborations of the project co-leaders, and through the three shared resource cores: Biospecimens Core, Biostatistics and Bioinformatics Core, and Administrative Core. The cores provide economy of effort and cost and support each of the projects. Finally to further enhance MM research and specifically the Aims of the 4 projects, this SPORE application supports novel translational studies through a Developmental Research Program (e.g., individual peptide monitoring by mass spectrometry to follow minimal residual disease), and through a mentored Career Development Program (e.g., developing novel immune therapies for MM) for young faculty. The historical and institutional commitment to MM research at Mayo Clinic is unequalled, and together with the leading role nationally and internationally in MM research of members of this SPORE we will be able to quickly translate our discoveries into new treatment strategies for patients with MM aimed not just at control, but ultimately to make cure become a reality.

Public Health Relevance

Most patients with multiple myeloma continue to die of the disease. This SPORE will develop new treatment approaches using oncolytic virotherapy and novel drugs that activate the immune system. In addition the SPORE will determine the clinical significance of mutations of the MYC locus, and recurrent point mutations in patients with multiple myeloma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA186781-01A1
Application #
8930229
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Ujhazy, Peter
Project Start
2015-09-01
Project End
2020-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Mayo Clinic, Arizona
Department
Type
DUNS #
153665211
City
Scottsdale
State
AZ
Country
United States
Zip Code
85259
Baughn, Linda B; Pearce, Kathryn; Larson, Dirk et al. (2018) Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. Blood Cancer J 8:96
Russell, Stephen J; Barber, Glen N (2018) Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines. Cancer Cell 33:599-605
Clay-Gilmour, Alyssa I; Kumar, Shaji; Rajkumar, S Vincent et al. (2018) Risk of MGUS in relatives of multiple myeloma cases by clinical and tumor characteristics. Leukemia :
Sidiqi, M Hasib; Aljama, Mohammed A; Muchtar, Eli et al. (2018) Light chain type predicts organ involvement and survival in AL amyloidosis patients receiving stem cell transplantation. Blood Adv 2:769-776
Nair, Shiny; Sng, Joel; Boddupalli, Chandra Sekhar et al. (2018) Antigen-mediated regulation in monoclonal gammopathies and myeloma. JCI Insight 3:
Msaouel, Pavlos; Opyrchal, Mateusz; Dispenzieri, Angela et al. (2018) Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects. Curr Cancer Drug Targets 18:177-187
Go, Ronald S; Rajkumar, S Vincent (2018) How I manage monoclonal gammopathy of undetermined significance. Blood 131:163-173
Kyle, Robert A; Larson, Dirk R; McPhail, Ellen D et al. (2018) Fifty-Year Incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, From 1961 Through 2010: A Population-Based Study With Complete Case Capture and Hematopathologic Review. Mayo Clin Proc 93:739-746
Calcinotto, Arianna; Brevi, Arianna; Chesi, Marta et al. (2018) Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat Commun 9:4832
Facon, Thierry; Dimopoulos, Meletios A; Dispenzieri, Angela et al. (2018) Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood 131:301-310

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