iStopMM
Introduction
What is iStopMM?
iStopMM is a prospective, population-based screening study for precursors of Multiple Myeloma, that aims to provide evidence on the optimal diagnostic approach and follow up for these diseases, particularly monoclonal gammopathy of undetermined significance (MGUS).1
Multiple Myeloma (MM) is a malignancy of plasma cells, and is always preceded by MGUS and Smouldering Multiple Myeloma (SMM).
Although MGUS is termed as a monoclonal gammopathy of “undetermined significance”, this precursor state of MM is associated with a reduced life expectancy. These patients are at risk of progression to Multiple Myeloma, with a rate of progression of around 1%1. In addition to progression to MM, MGUS patients have higher risk of infections, osteoporosis, fractures, kidney and heart disease and thrombosis2,3, and this can lead to increased risk of death.
There are indications that patients known to have MGUS have a better prognosis when they progress to MM compared to patients first identified with an active MM, since prior knowledge of MGUS may lead to a more frequent follow-up and, as a consequence, an earlier diagnosis and intervention in patients that progress to MM4,5. However, MGUS is normally asymptomatic and is identified only by coincidence as patients are investigated for some other unrelated illness.
iStopMM stands for Iceland Screens, Treats or Prevents Multiple Myeloma.
Why is it important?
The iStopMM trial is a prospective study that aims to evaluate the impact of actively screening for MGUS, and if the knowledge of MGUS condition could lead to an improvement in overall survival for these patients
All Icelanders over the age of 40 were invited to participate in the iStopMM study; which commenced in September 2016. Approximately 80,000 individuals consented to take part to this study, for a total participation rate of about 50% of the Icelandic population over the age of 40. The process involved the collection of a blood sample; this was used to identify the presence of monoclonal proteins produced by the clonal expansion of plasma cells.
The Binding Site is a proud collaborator of this study, and almost 80,000 samples were sent to our laboratories in Birmingham, UK, where they were screened for a monoclonal protein using serological methods.1,a,b,
If a person was identified as having MGUS as part of the iStopMM study, they were considered eligible for a randomized trial of follow-up strategies with 3 longitudinal arms. The testing identified 3,487 MGUS patients and these were randomized into the three arms in the study, evenly distributed with regard to patient characteristics such as age, gender and mean monoclonal protein concentration.6
The data collected will indicate the best follow-up strategy for patients identified as having an MGUS, also addressing the psychological burden from the knowledge of a pre-cancerous condition in the patients.
The study will also evaluate the potential benefits of close monitoring for individuals with MGUS identified by screening, to help identify those at highest risk of progression and allow for early intervention, if necessary, to improve the treatment outcomes.7,d,e
Overall, the iStopMM study provides important insights into the prevalence and natural history of MGUS, as well as the potential benefits of a population-based screening and early intervention. However, further research is needed to determine the optimal screening strategies and interventions for individuals with MGUS.1,f,g
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Abbreviations and Acronyms
| Definitions | |
|---|---|
| iStopMM | Iceland Screens, Treats or Prevents Multiple Myeloma |
| IFE | Immunofixation |
| MM | Multiple myeloma |
| MGUS | Monoclonal gammopathy of undetermined significance |
| SMM | Smouldering Multiple Myeloma |
| sFLC | Serum free light chains |
| SPEP | Serum protein electrophoresis |
3rd Party Websites
- https://www.myeloma.org/blog/key-takeaways-ash-2022
- https://clinicaltrials.gov/ct2/show/NCT03327597
- https://istopmm.com/the-study/
- https://www.myeloma.org/black-swan-research-initiative/istopmm
- https://opinvisindi.is/bitstream/handle/20.500.11815/3972/S%C3%A6mundur%20R%C3%B6gnvaldsson-me%C3%B0%20greinum.pdf?sequence=1&isAllowed=y
- https://clinicaltrials.gov/ct2/show/NCT03327597?term=NCT03327597&draw=2&rank=1
- https://www.myeloma.org/black-swan-research-initiative/istopmm
References
- Rögnvaldsson S, et al. Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies. Blood Cancer Journal 2021; 11:94
- van de Donk NW, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica 2014; 99:984-996
- Kristinsson SY, et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study. Haematologica 2009; 94:1714-1720
- Sigurdardottir E, et al. The role of diagnosis and clinical follow-up of monoclonal gammopathy of undetermined significance on survival in multiple myeloma. JAMA Oncology 2015; 1:168-174
- Go RS, et al. Determining the clinical significance of monoclonal gammopathy of undetermined significance: a SEER-medicare population analysis. Clin Lymphoma Myeloma Leuk 2015; 15:177-186
- Kristinsson SY, et al. Screening for Monoclonal Gammopathy of Undetermined Significance: A Population-Based Randomized Clinical Trial. First Results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study. Blood / Presented at ASH 2021; 138:156a
- Einarsson Long T, et al. Defining New Reference Intervals for Serum Free Light Chains in Individuals with Reduced Kidney Function: Results of the Population- Based on Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) Study. Blood / Presented at ASH 2021; 138:542a