The iStopMM Study on Transient M-Proteins and the Use of Mass Spectometry for the Evaluation of Monoclonal Proteins

Dr. Robert Palmason discusses the epidemiology of individuals with transient M-proteins in the prospective screening manner based on the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study

Abstract title:

Transient M-Proteins: Epidemiology, Causes, and the Impact of Mass Spectrometry: The iStopMM Study

Purpose of the trial:

Among clinicians, it is well-known that the identification of a monoclonal(M) protein may disappear at a later timepoint (transient M protein) after certain infections, in the setting of some automimmune conditions, or other conditions. However, there is no information from a systematic study investigating patterns of transient M-proteins in a prospectively monitored cohort.The aim of this large, population-based study was to describe the epidemiology and characteristics of individuals with transient M-proteins in the prospective screening manner based on the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study. Furthermore, given the recent introduction of highly sensitive mass spectrometry (MS) based assays for the identification and quantification of M proteins, we were motivated to investigate whether transience is also related to an increased sensitivity of the assay used in a comparison with conventional serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE).

Video summary:

The iStopMM study is an ongoing nationwide screening study for multiple myeloma precursors in Iceland. A total of 75,422 Icelanders ≥40 years old (51% of the population) were screened for M protein using SPEP and free light chains. Participants with a detectable M-protein entered a randomized controlled trial with three arms where arms 2 and 3 underwent initial testing and longitudinal follow-up. The transient M-protein cohort was defined as individuals with a positive SPEP who at a later timepoint returned a negative SPEP/IFE sample. Comorbidity data and prescription medicine use was acquired from three high-quality national disease and prescription medicine registries. MS (EXENT®, Binding Site, Birmingham, UK) analyses were performed on the original diagnostic sample and a follow-up sample with a cutoff of 0,02g/L considered as positive. We evaluated comorbidity and medication use comparing individuals with transient M protein to age- and sex-matched subjects with persistent M protein in a 4:1 matched nested case-control study. Overall, the iStopMM MGUS cohort comprises 3,358 individuals. Of those 2,037 underwent annual follow-up testing. A total of 198 (9.8%) individuals were identified as having transient M protein according to SPEP and IFE.

Conclusion:

In this large prospective study we found that M proteins were transient in almost 10% of cases. Using a more sensitive MS, the proportion of transient M proteins was only 2.6%. Thus, most of individuals with transient M proteins based on SPEP/IFE are falsely negative, when using MS as the benchmark. Our prospective cohort study provides novel insights on longitudinal patterns of abnormal serum proteins, it highlights how the use of MS results in the identification of low M proteins, and it shows that transient M proteins are often only below the limit of detection with conventional SPEP/IFE.

Trial information: 

ASH 2022: Abstract #967 (https://ash.confex.com/ash/2022/webprogram/Paper164758.html)

Authors:

Robert Palmason, MD, Oscar Berlanga, PhD, Jon Kristinn Sigurdsson, Sæmundur Rögnvaldsson, MD5,, Sigrun Thorsteinsdottir, MD, PhD, Sara Ekberg, PhD, Michael Crowther, PhD, Marina Levy, Elin Ruth Reed, Jon Þórir Oskarsson, MSc, Gudrun Asta Sigurdardottir, Brynjar Vidarsson, MD, Pall Torfi Onundarson, MD, Bjarni Agnar Agnarsson, MD, Margret Sigurdardottir, MD, Ingunn Thorsteinsdottir, MD, PhD6*, Signy Vala Sveinsdottir, MD PhD6*, Fridbjorn Sigurdsson, MD10*, Isleifur Olafsson, MD, PhD, 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, Ingigerdur Solveig Sverrisdottir, MD, BSc, Hlif Steingrimsdottir, MD, Thorir Einarsson Long, MD, PhD, Malin Hultcrantz, MD, PhD, Ola Landgren, MD, Stephen Harding, PhD, Brian G.M. Durie, MD, Thorvardur Jon Love, MD, PhD and Sigurdur Y Kristinsson, MD, PhD