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152 High Prevalence of Monoclonal Gammopathy in a Population at Risk: The First Results of the Promise Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 652. Multiple Myeloma and Plasma cell Dyscrasias: Clinical and Epidemiological: Monoclonal Gammopathies of Determined Significance: What We Have and What We Want
Hematology Disease Topics & Pathways:
Adults, Plasma Cell Disorders, Diversity, Equity, Inclusion, and Accessibility (DEI/DEIA) , Diseases, Disparities, Lymphoid Malignancies, Technology and Procedures, Study Population, Diversity, Equity, and Inclusion (DEI), Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.), Serologic Tests
Saturday, December 11, 2021: 12:15 PM

Habib El-Khoury, MD1,2, Jean-Baptiste Alberge, PhD1,2,3*, Hadley Barr1,2*, Ciara Murphy1,2*, D.J. Sakrikar, PhD4*, Tara Krause, MSc4*, David Barnidge, PhD4*, Mark Bustoros, MD5, Houry Leblebjian, PharmD, BCOP6*, Annie Cowan, BS1,7*, Maya Davis, BA1,2*, Julia Amstutz1,2*, Jacqueline Perry, MPH1,2*, Cody J. Boehner, BS1,2*, Elizabeth D. Lightbody, PhD1,2*, Tarek H Mouhieddine, MD1,8,9, Romanos Sklavenitis-Pistofidis, MD2,3,10, Mark C Perkins, PhD11*, Stephen Harding, PhD11, Prashant Kapoor, MD12, Clifton C. Mo, MD1,2, David L. Murray, MD, PhD13*, Ivan M. Borrello, MD14, Gad Getz, PhD3,15,16*, Timothy R Rebbeck, PhD1,17*, Catherine R. Marinac, PhD1,17,18 and Irene M. Ghobrial, MD1,2,3,18

1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
2Harvard Medical School, Boston, MA
3Broad Institute of MIT and Harvard, Cambridge, MA
4The Binding Site Inc., Rochester, MN
5Division of Hematology & Medical Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY
6Department of Pharmacy, Dana-Farber Cancer Institute, Boston, MA
7Alix School of Medicine, The Mayo Clinic, Rochester, MN
8Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
9Harvard Medical School, Cambridge, MA
10Department of Medical Oncology, Dana-Farber Cancer Institute, Brookline, MA
11The Binding Site Inc., Birmingham, United Kingdom
12Division of Hematology, Mayo Clinic, Rochester, MN
13Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
14Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
15Center for Cancer Research, Massachusetts General Hospital, Boston, MA
16Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA
17Harvard T.H. Chan School of Public Health, Boston, MA
18The Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA

Background

Multiple myeloma (MM) evolves from monoclonal gammopathy of undetermined significance (MGUS), a clinically detectable but asymptomatic premalignant phase seen in ~3% of the general population 50 years of age or older. The prevalence of MGUS has not been described in a population at high risk of developing MM, specifically Black/African American (AA) individuals or first-degree relatives of patients with hematologic malignancies (HM). In 2019, we launched the first nationwide US screening study for individuals at high risk of MM to help better identify what population would benefit most from screening and early intervention for precursor MM stages. We aim to assess the prevalence of MGUS in a population at high risk of MM and characterize clinical variables of individuals who screen positive. Here, we report interim screening data on the first 2,960 participants.

Methods

Individuals aged 40 or older with an additional MM risk factor are eligible to be screened in the PROMISE Study. High-risk individuals include Black/AAs and those with a first-degree relative diagnosed with a hematologic malignancy or a precursor condition to MM. Blood from all participants was analyzed via serum protein electrophoresis, immunofixation, and Optilite® to measure the serum free light chains (sFLC), IgG, IgA and IgM. Results were returned to all participants, and those who tested positive for a monoclonal gammopathy (MGUS/SMM) were referred to a hematologist for clinical follow-up and invited to periodically complete epidemiologic exposure and psychosocial questionaries, including a 4-item cancer worry questionnaire and the RAND 36-item Short Form Survey (SF-36).

To investigate the use of the higher-sensitivity matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) with the Optilite® IgG, IgA, IgM and sFLC results as a screening test for all participants, we rescreened 1,092 samples from PROMISE. The Binding Site Group proprietary software was used for the analysis of the combined MS/Optilite® results, allowing for the detection and quantification of M-protein. Heavy-Chain MGUS (HC-MGUS) was defined by the presence of one or more paired heavy and light chain monoclonal peaks detected by MS. Pairing was based on mass to charge ratio of identified peaks.

To enrich the PROMISE cohort with Black/AA individuals, we identified and screened 1,868 Black/AA additional individuals from the Mass General Brigham (MGB) Biobank who met the PROMISE enrollment criteria. Screening was performed by MS/Optilite®, and results have not been returned to participants.

Results

We screened 2,960 participants with the combined MS/Optilite® approach. We report here the prevalence of HC-MGUS and plan on presenting the estimated rate of light chain MGUS in our cohort, at the meeting. We detected HC-MGUS in 9.6% (95% CI: 8.6-11%) of our cohort, with a prevalence of 10% (95% CI: 8.3-12%) in the PROMISE cohort and 9.4% (95% CI: 8.1-11%) in the MGB cohort (Table 1 and Figure 1). HC-MGUS prevalence increased with age in high-risk individuals from 4.9% (CI: 3.3-6.9%) for participants aged 40-49 to 13% (CI: 10-17%) in the 70-79 range (P < 1.2E-5). Among monoclonal HC-MGUS, we found 65% IgG, 18% IgM, and 18% IgA. M-spike was quantified in 97% of samples. Median M-spike concentration was, 0.058g/dL (max. 2.6g/dL) for IgG, 0.0043g/dL (max. 0.6g/dL) for IgM, and 0.067g/dL (max. 0.8g/dL) for IgA.

In the Promise cohort, no significant change in cancer worry was observed across the pre- and post-screening interval among participants who screened positive (P = 0.52). Health-related quality of life, as measured by the SF-36, was not significantly different in screen-positive vs. screen-negative individuals for any of the eight subscales (all P > 0.20).

Conclusions

We present the largest dataset on monoclonal gammopathy prevalence and screening in individuals at high risk for MM, and more specifically the largest cohort of Black/AA, using a novel high-sensitivity testing approach. Our results confirm that older adults who are Black/AA or have a first-degree relative with an HM have a high prevalence MGUS and may benefit from precision screening approaches to allow for early detection and clinical intervention. Preliminary data on cancer worry and quality of life indicates that the psychosocial burden of screening in this population is likely minimal.

Disclosures: Sakrikar: The Binding Site: Current Employment. Krause: The Binding Site: Current Employment. Barnidge: The Binding Site: Current Employment. Bustoros: Takeda: Consultancy, Honoraria; Janssen, Bristol Myers Squibb: Honoraria, Speakers Bureau. Perkins: The Binding Site: Current Employment. Harding: The Binding Site: Current Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kapoor: Ichnos Sciences: Research Funding; Amgen: Research Funding; Pharmacyclics: Consultancy; Takeda: Research Funding; Sanofi: Consultancy; Regeneron Pharmaceuticals: Research Funding; AbbVie: Research Funding; BeiGene: Consultancy; Sanofi: Research Funding; Karyopharm: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Consultancy; Cellectar: Consultancy. Mo: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Eli Lilly: Consultancy; Janssen: Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Murray: The Binding Site: Patents & Royalties: Potential Royalties for use of mass spectrometry in M-protein detection. Getz: Scorpion Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; IBM, Pharmacyclics: Research Funding. Marinac: GRAIL Inc: Research Funding; JBF Legal: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy.

*signifies non-member of ASH