Contrary to current insight, the incidence of monoclonal gammopathy of undetermined significance (MGUS) was similar between ethnicities, according to a study that compared the epidemiology of MGUS in the southern African country of Eswatini to results of a previous study of a mainly white cohort in Minnesota’s Olmsted County the U.S.1 The study was published in JNCI Cancer Spectrum.
“We were a bit surprised to find the prevalence of conventional MGUS to be similar between Eswatini and Olmsted County, as prior studies have repeatedly demonstrated higher rates of monoclonal gammopathies within Black compared to white populations in America,” said author Kara Cicero, MD, MPH, of Fred Hutchinson Cancer Center in Seattle.
Multiple myeloma and its precursor MGUS have only been thoroughly studied in white populations. The researchers aimed to describe the prevalence of MGUS in Eswatini and compare their results to those from the landmark epidemiology study of a 97.3% white population in Olmsted County.2
The researchers created a nationally representative biorepository of 13,339 Eswatini residents. Individuals had participated between 2016 and 2017 in the Swaziland HIV Incidence Measurement Survey.1 The researchers randomly selected and tested 515 plasma samples for MGUS. These patients had a median age of 50 years (range = 35-80), and 60% were female. Of the 38.6% who were HIV-positive, 82.4% were on antiretroviral therapy (ART). MGUS was defined using the same criteria as the Olmsted County study.
The prevalence of MGUS stood at 13.2% (n=68) in Eswatini. Of the cases, 84% (n=57) were light-chain isotype. The Olmsted County cohort included only individuals older than 50. For this age group, the rate of MGUS in Eswatini was 15.6%, which is 3.7 times greater than the prevalence reported in Olmsted County (p<0.0001). Notably, the prevalence of conventional MGUS was 3.4% in Eswatini, which is similar to the 3.2% to 3.4% previously reported in Olmsted County. However, the prevalence of light-chain MGUS was more than 13 times higher in Eswatini than Olmsted County, at 12.3% versus 0.8%, respectively.
“Our study elicits further questions than answers. MGUS has been thought to disproportionately affect populations of African descent, but perhaps this reflects environmental disparities rather than any differences attributed to ethnic ancestry,” Dr. Cicero said.
In Eswatini, individuals with HIV who were not on ART were more likely to have MGUS. Specifically, HIV status was not significantly associated with MGUS (odds ratio [OR] = 1.05; 95% CI 0.62-1.77), and MGUS occurred less frequently for those on ART (adjusted OR=0.31; 95% CI 0.11-0.82). The odds of MGUS rose by 2.4% with each year of age (p=0.02), but sex and economic status were not associated with MGUS.
A post-hoc analysis of the prevalence of MGUS in Eswatini was conducted using the Icelandic group’s proposed revision for the definition of light-chain MGUS presented at the American Society of Hematology’s 2023 annual meeting.3 When applying the algorithm by Thorir Einarsson Long, MD, PhD, and colleagues, the prevalence of MGUS dropped to 3.11% (n=16), with light-chain MGUS comprising 31% of these cases. The prevalence of light-chain MGUS fell by 76%, from 57 to five cases.
“Our study also questions the current definition of light-chain MGUS, whereby abnormal free light-chain ratios with elevations in the appropriate light chain may be confounded by factors unrelated to clonality, such as chronic inflammation stimulating a monotypic process; Long et al.’s revised Icelandic diagnostic criteria of light-chain MGUS may be one way to increase specificity of this entity,” Dr. Cicero said. “Finally, the association between MGUS and ART, but not CD4 count or viral load, among those living with HIV is quite interesting and begs further investigation.”
Limitations to the study include the analysis of plasma rather than serum, which is used in clinical practice to detect monoclonal gammopathy. Another limitation comprised the historic cohort that served as the comparison group. Further, the deidentified nature of the biorepository prevented further laboratory testing, bone marrow biopsies, and longitudinal follow-up.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Cicero KI, Dlamini X, Mavengere Y, et al. Prevalence of monoclonal gammopathy of undetermined significance in Eswatini: a population-based study in Africa [published online ahead of print, 2024 July 11]. JNCI Cancer Spectr. doi: 10.1093/jncics/pkae056.
- Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362-1369.
- Long TE, Rögnvaldsson S, Thorsteinsdottir S, et al. Revised definition of free light chains in serum and light chain monoclonal gammopathy of undetermined significance: results of the Istopmm Study. Blood. 2023;142(Suppl 1):535.
