Taking a Deeper Dive into the IMF's iStopMM Study
Principal Investigator Sigurður Yngvi Kristinsson, MD, PhD provides insights on the iStopMM Project and delves into why the ambitious research trial is headed toward finding a cure for myeloma.
If you are part of the IMF’s myeloma community, you have probably heard of our iStopMM® trial. In this week’s blog, we’ll take a deep dive into what makes this study so unique and important.
What is the iStopMM Project?
iStopMM stands for Iceland Screens, Treats, Or Prevents Multiple Myeloma
Started in 2016 and officially launched in 2017, iStopMM is an ambitious research project that is currently ongoing at the University of Iceland in Reykjavik, Iceland.
The project is being led by Principal Investigator Sigurður Yngvi Kristinsson, MD, PhD (Professor of Hematology, University of Iceland — Reykjavik, Iceland) and supported by the International Myeloma Foundation (IMF).
The goal of iStopMM is to screen Iceland’s population for the presence of monoclonal gammopathy of undetermined significance (MGUS) — the precursor state to smoldering multiple myeloma (SMM) — or for the presence of smoldering myeloma (SMM), or active myeloma.
The Purpose of iStopMM
“The iStopMM trial has one mail goal, and that is to evaluate the impact of screening for the multiple myeloma precursor, which is called MGUS. To do that, we asked all Icelanders eight years ago aged 40 years and older at that time to participate in the study — we got more than 54% of the whole Icelandic population to join. Since then, we have gathered more than 75,000 samples and screened them for the precursor. And it turns out that almost 5% of the Icelandic population has the precursor MGUS,” said Dr. Kristinsson.
“The iStopMM study is the largest nationwide clinical trial of any cancer precursor ever performed in the world” with the goal of “diagnosing the individual at the MGUS phase to be able to treat them at the smoldering myeloma phase and prevent them from ever developing myeloma,” added Dr. Kristinsson.
“The high participation rate really tells us that this study is unique and important and will be representable to other countries as well,” he further stated.
Why Iceland?
According to Dr. Kristinsson, Icelandic healthcare data is so well-organized, clinicians have information on every medical diagnosis, every prescription, every cancer, and every comorbidity of the 80,000 individuals who had been diagnosed before the study began, as well as that same data for all individuals followed up through the study.
Also, Iceland is home to deCODE Genetics. This company has performed whole-genome sequencing for the entire population of Iceland. By collaborating with deCODE Genetics, the iStopMM study has access to this data, creating the unique opportunity to evaluate risk factors for MGUS and the role of germline genetics/hereditary. So, researchers can consider both the risk of getting MGUS as well as factors affecting the course of the disease.
How Has the iStopMM Study Been Conducted So Far?
After screening over 75,000 samples to determine who had MGUS, results revealed that nearly 5% of the Icelandic population had the myeloma precursor.
Once the study determined who had MGUS, these individuals were randomized into three different arms:
Arm 1) No further follow-up is required.
Arm 2) Enhanced testing will be conducted.
Arm 3) Interventions will be made as appropriate.
The iStopMM study has a protocol that is strictly followed with all three arms, which means every participant is managed in the same way according to the arm.
Why Is iStopMM So Important and Unique?
With its high participation rate of more than 50 percent, this study tells a story of how MGUS and myeloma affect populations in other countries as well. Patients in the iStopMM study are followed and their data is cross-referenced with other countries’ registries.
Dr. Kristinsson explains, “We have pretty much 100% coverage of all diseases, medications, and so on, of the participants in the study. This is why the study cannot be done in any other country while the results and findings are totally generalizable to other populations.”
Furthermore, the study determines if early diagnosis of MGUS is beneficial. Dr. Kristinsson said, “We have seen in clinical studies performed in other cancers, like breast cancer, cervical cancer, and other cancers. This has not been done in MGUS or myeloma. This is what we are doing in real life: evaluating if we should screen for MGUS or not.”
Another important aspect of iStopMM is the biobank. Every time samples of blood, urine, or bone marrow are collected, they are placed in a biobank for future use. This biobank is accessible not just by the study, but by the broad scientific community.
iStopMM’s Early Findings: Changing the Face of Myeloma
According to Dr. Kristinsson, “Our early findings show that we are really changing the face of myeloma by early detection and early intervention. We see in our studies that clinical symptoms and signs of people diagnosed with myeloma that have not been screened: they have more kidney disease; more bone lesions, more fractures; and they’re diagnosed earlier than people who show up with a full-blown malignancy. So, we’ve already changed people’s lives! These are the individuals who have SMM that we have detected and treated early.”
Also, the iStopMM study looks at the impact of screening and how participants react to an MGUS diagnosis. It delves into the effects of a diagnosis on a patient’s mental health and quality of life. This facet is another unique and informative aspect of the study.
“What we hope to do is to prove this approach works and take it to other countries to show that it can be done,” said Dr. Kristinsson, emphasizing that screening and detection of MGUS is possible, and that early treatment is feasible and effective.
Why Should iStopMM Be Funded?
“It's tremendously important since we have reached the stage in myeloma research that we know early intervention is beneficial, we know that. We know it prolongs progression to myeloma, and we know it prolongs overall survival. However, less than 5% of myeloma patients are ever diagnosed at the smoldering or precursor state,” said Dr. Kristinsson.
“So, in real life we can never treat them early, most individuals. This is why a study like this is desperately needed. We need to know if we detect everyone with MGUS, follow them over time and intervene early. Then, we can prevent them from getting myeloma with all its terrible complications,” he further stated.
Dr. Kristinsson also emphasized the importance of new and novel drugs. “I think that one of the major improvements in myeloma care through recent years is novel drugs. So, these new drugs have been able to turn this disease from an overall survival around two to three years, to an overall survival that is now more than10 years. This is a key aspect of myeloma care.”
“However, we need to do better, because when almost every one of these individuals are diagnosed with myeloma, they already have complications of the disease. They may have fractures, blood deficiency, kidney disease, or repeated infections. We need to find these individuals before all that happens and then treat them with all the fancy drugs. To be able to cure myeloma, early detection, early intervention, and new drugs are key.”
iStopMM is also bringing together the global myeloma community of leading researchers. The IMF’s International Myeloma Working Group (IMWG) has gathered doctors and other healthcare practitioners to present and discuss data from the iStopMM study. These experts facilitate collaboration worldwide.
Make an Impact on Finding a Cure
If you are able to do so, consider how your gift to the IMF can impact our path to a cure through projects like iStopMM. When you begin thinking about your philanthropic engagement with the IMF, please contact Sylvia Dsouza, IMF Vice President, Development at [email protected] or (818) 487-7455 x268, to start a conversation.
