MGUS Cases with Multiple Paraproteins

Dr. Sæmundur Rögnvaldsson presents the results of the first large and prospective examination of MGUS cases with multiple paraproteins. 

Abstract title:

Monoclonal Gammopathy of Undetermined Significance (MGUS) with Multiple Paraproteins: Results from the Population-Based Istopmm Screening Study

Purpose of the trial:

Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma and related disorders and is marked by the presence of monoclonal immunoglobulins, also known as paraproteins, in the serum, as shown by protein electrophoresis tests. Prior small studies have reported that in 3% of MGUS cases, more than one paraprotein is present, but the implications and biology of these multiple paraproteins (MP) are unclear. Our study is the first large and prospective examination of MGUS cases with MP.

Video summary:

Data were acquired from the ongoing iStopMM study, a population-based screening study for MGUS and randomized trial of follow-up strategies. A total of 75,422 Icelanders over 40 years old were screened for MGUS by SPEP and IFE. Two-thirds of those with MGUS were randomized to further evaluation and follow-up.

Participants with a paraprotein on SPEP and IFE were included in the study. Those with previous MM or related disease, paraprotein ≥3.0 g/dL, or an involved to uninvolved free light chain (FLC) ratio ≥100 were excluded. Those who had more than one monoclonal peak on IFE at baseline were defined as having MP. Baseline characteristics of those with MP and a single paraprotein were then compared. In participants who were followed at the study clinic, rates of progression to MM, smoldering MM (SMM), Waldenström macroglobulinemia (WM) and other related disorders were compared using logistic regression, adjusting for age.

Conclusions:

In this large, population-based screening study with 75,422 participants, we found MP to be more common in MGUS (9.4%) than previously observed, and to be associated with older age and male sex. IgM paraproteins were more common in those with MP and were associated with a higher number of paraproteins. Over half of those with MP were later found to a have a single paraprotein, and 42% of paraproteins were not observed again during follow-up. During a median of 4 years of follow-up, none with MP developed MM. We speculate that MP could in some cases be caused by a strong or defective but transient immune response and could be associated with lower risk of MGUS progression. Interestingly, we observed multiple abnormal monoclonal plasma cell populations in some with MP, but whether they develop from the same insult or independently is not clear.

With the advent of mass spectrometry-based diagnostics the rate of MP is expected to increase significantly. Understanding their clinical implications and biology will therefore become more important in guiding clinical practice. Mass spectrometry results for this cohort are pending and will shed more light on the prevalence, implications, and underlying biology of MP in MGUS.

Trial information:

ASH 2022: Abstract #4504 (https://ash.confex.com/ash/2022/webprogram/Paper168070.html)

Authors:

Sæmundur Rögnvaldsson, MD, Jon Þórir Oskarsson, MSc, Sigrun Thorsteinsdottir, MD, PhD, Elin Ruth Reed, Gudrun Asta Sigurdardottir, Brynjar Vidarsson, MD, Pall Torfi Onundarson, MD, Margret Sigurdardottir, MD, Bjarni Agnar Agnarsson, MD, Isleifur Olafsson, MD, PhD, Ingunn Thorsteinsdottir, MD, Signy Vala Sveinsdottir, MD PhD, Robert Palmason, Fridbjorn Sigurdsson, MD, Asdis Rosa Thordardottir, Elias Eythorsson, MD, PhD, Asbjorn Jonsson, MD, Runolfur Palsson, MD, Olafur Skuli Indridason, MD, MHS, Thor Aspelund, PhD, Gauti Gislason, Andri Olafsson, Jon Kristinn Sigurdsson, Ingigerdur S Sverrisdottir, MD, Gudlaug Katrin Hakonardottir, Thorir Einarsson Long, MD, PhD, Ragnar Danielsen, MD, Malin Hultcrantz, MD, PhD, Brian G.M. Durie, MD, Stephen Harding, PhD, Ola Landgren, MD, Thorvardur Jon Love, MD, PhD and Sigurdur Y Kristinsson, MD, PhD