Key early results from iStopMM project presented at 4th Annual Meeting in Reykjavik, Iceland

REYKJAVIK, Iceland, November 14, 2019—After three years of work, initial results from the IMF-supported iStopMM project were presented here today by Dr. Sigurdur Kristinsson (University of Iceland) and his team at the 4th annual iStopMM meeting. The acronym iStopMM stands for Iceland Screens, Treats, or Prevents Multiple Myeloma.

The team, which has grown to 20 members, delivered early results at the iStopMM headquarters’ deCODE genetics facility. The results of everyone’s hard work are already very impressive. The project’s main goal is to assess the impact and outcomes from early screening for MGUS, smoldering myeloma, and active myeloma for the whole of Iceland. The participation rate (approximately 80,000 adults over age 40 volunteered to take part) has been huge, producing the largest screening project for any type of cancer ever conducted.

Early results summary 

As Dr. Kristinsson emphasized, these results are still “super preliminary,” but it is possible to see several trends.

• Psychological impact
  What is the psychological impact of the screening process? How do individuals react to the discovery of a previously unknown MGUS (or SMM or MM)? The level of anxiety and depression among this group actually decreased slightly during the early follow-up. Meeting with the project’s nurses, who explain the significance of the findings and, in some cases, the lack of any active disease at that moment in a patient, may confer a degree of reassurance. The main goal of this study was to exclude the possibility of any high level of induced anxiety, which, fortunately, did not occur. Further follow-up will be important.

• Baseline testing 
  As part of the iStopMM study protocol, one-third of the patients with MGUS undergoes a very detailed baseline testing, including bone marrow evaluation and whole-body CT scanning. Currently, the standard procedure is to simply monitor patients with very low-level MGUS. However, in this study the bone-marrow testing revealed that 16% of the MGUS patients actually had SMM—a higher level of disease, which requires closer monitoring. This finding will most likely be practice-changing, meaning that bone-marrow testing does need to be performed for MGUS patients at baseline.

  In addition, 16 patients have been discovered to have previously unknown active myeloma needing consideration of treatment. The overall results of the over 1,000 bone-marrow tests performed to date—plus linked imaging results—are now being collated and assessed. 

• Biobank
  A strong part of this project is the enormous biobanking activity. Samples of blood, bone marrow, and urine are collected from patients for future use. In addition, full genetic information is available for all patients. As patients’ natural history evolves over time, there will be endless opportunities for biologic cross-correlations. Which patients remain stable? Which patients progress? 

  An amazing baseline observation is that patients with MGUS have a poorer expected survival versus those without MGUS, independent of whether SMM or MM subsequently develops. Why is that? And what really impacts the outcome for a patient with MGUS? There are huge opportunities for interventions and prevention strategies.

• Specialized testing of bone marrow and blood 
  The iStopMM team has been using the Spanish/EuroFlow methods for immune detection and classification. This is the next-generation-flow (NGF) cytometry method developed as part of the IMF’s Black Swan Research Initiative. The Iceland team has demonstrated that the presence of myeloma cells in the blood is a poor prognostic feature, indicating more active disease and higher likelihood of disease progression. This—together with the results from the Spanish Black Swan Research project—underscores the fact that blood-monitoring using the NGF method is extremely useful and avoids the need for repeated bone-marrow testing—a big relief for patients. 

  Detailed testing of immune micro-environment cells is also being conducted by the iStopMM team in collaboration with the University of Salamanca team. Full details will be available soon.

• Light-chain MGUS
  Some patients only have an abnormal free light chain (FLC) ratio.  Do they have a true monoclonal gammopathy (MGUS) or not? As part of the iStopMM project, The Binding Site has been performing mass spectrometry to determine if a light chain monoclonal protein is present or not. For uncertain cases, mass spectrometry will become a key test to give a definite answer.

• Early intervention treatment strategies
  The early intervention treatment strategies are just beginning to be implemented in the iStopMM project. It is too early to provide any meaningful outcomes beyond saying that all is going well.

• High-risk smoldering myeloma
  Another important early observation from the iStopMM research is that the current classification and scoring systems for HR-SMM do NOT cross-correlate well. A patient deemed high-risk by the Spanish system may not be high-risk by the new 2/20/20 method or the total points scoring system. This further underscores the main point in my recent blog about SMM, namely that treatment intervention, such as with lenalidomide, cannot be considered a “standard of care” since we do not yet have a secure enough routine diagnosis of high-risk status. Ongoing trials and follow-up are required, and early, serial monitoring (a dynamic assessment) is a prudent approach as a first step.

BOTTOM LINE 

As always, it was a great pleasure to visit with the iStopMM team and it was extremely exciting for the IMF team (President Susie Durie, Vice-President Support Groups Robin Tuohy, her husband, patient Michael Tuohy, and me) to hear these early findings. The results from this research will impact all aspects of myeloma care for the future, including:

• Screening: Is it recommended and safe? Probably yes.
• Baseline diagnosis: New classification systems for MGUS and SMM will undoubtedly emerge. We will know which patients to monitor and how, as well as which patients to treat early and with what.

In the coming years, the findings from this ambitious project will, without a doubt, transform the approach to diagnosis and management of plasma cell disorders.

Dr. Brian G.M. Durie founded and now serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.