[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.175.200.4. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 1,452
Citations 0
Original Investigation
July 18, 2019

Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

Author Affiliations
  • 1Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Division of Cancer Epidemiology and Genetics, Biostatistics Branch, National Cancer Institute, Rockville, Maryland
  • 3Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen’s University, Belfast, Northern Ireland, United Kingdom
  • 4Division of Hematology, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
  • 5Multiple Myeloma Section, National Cancer Institute, Bethesda, Maryland
  • 6Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 7Department of Hematopathology, Memorial Sloan Kettering Cancer Center, New York, New York
  • 8Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • 9Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
  • 10Myeloma Section, Department of Medicine, University Hospital of Malmo, Malmo, Sweden
JAMA Oncol. Published online July 18, 2019. doi:10.1001/jamaoncol.2019.1568
Key Points

Question  Are changes in serum immune marker results associated with disease progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma?

Findings  In this cohort study of 685 individuals with a diagnosis of progressing or stable MGUS, in longitudinal analysis of individuals with serial samples prior to progression, 23 of 43 (53%) had high-risk MGUS before progression, and 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS to multiple myeloma within 5 years; similar results were found for light-chain MGUS. Evolving monoclonal proteins, serum-free light chains, and immunosuppression were associated with disease progression.

Meaning  These findings support annual blood testing and risk assessment for all individuals with MGUS or light-chain MGUS.

Abstract

Importance  Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup.

Objective  To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS.

Design, Setting, and Participants  This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018.

Main Outcomes and Measures  Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured.

Results  Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P = .04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P < .001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P < .001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P < .001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P < .001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P < .001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.

Conclusions and Relevance  The findings of evolving risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.

×