iStopMM: Investigators From Iceland Report First Results of Population-Based Screening for Multiple Myeloma

Before the blood cancer multiple myeloma (MM) develops, clinicians can detect precursor conditions, called monoclonal gammopathy of undetermined significance (MGUS), or related lymphoproliferative disorders (LP). If patients are diagnosed at this stage, the chances of survival are greatly improved. But less than 5% of cases are caught at this stage.

Five years ago, investigators in Iceland led by Sigurdur Kristinsson, MD, PhD, of the University of Iceland sought to evaluate what would happen if screening for MGUS were widely available—would it lead to an improvement in overall survival?

They launched the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, which is described as “the first population-based screening study for MGUS that includes a randomized clinical of follow-up and treatment strategies.”¹

Early results from iStopMM were presented in 4 abstracts last week during the 2021 American Society of Hematology Annual Meeting and Exposition, held in Atlanta and online.

In a video prepared for the International Myeloma Foundation, Kristinsson outlined the scope and mission of the project. “No one has ever done anything like this before—ever,” he said.² Public support for and participation in the project has been tremendous, he said. “The president of Iceland was the first to give informed consent.”

The project is gathering next-generation sequencing (NGS) data on all those screened, which will be invaluable in researching biomarkers for MM and possibly other blood cancers. Another important aspect of the trial, Kristinsson explained, is tracking participants’ quality-of-life scores; thus far, it appears that having a positive screen for MGUS does not detract from quality of life.²

Although early results are “encouraging” and show that following patients with detected MGUS closely does yield more positive diagnoses, investigators are cautious. “Until final results of the iStopMM study become available, including data on survival and quality of life, we advise against systematic MGUS screening in healthy individuals,” they wrote.

According to the study authors, iStopMM was open to all Iceland residents born before 1976. Of the 148,708 eligible residents, just over half (54.3%, 80,759) provided consent for screening, and serum samples were collected over a 4-year period through the end of 2020. Investigators were able to collect samples from 75,422 people (93.4%) who provided their initial consent.

Samples were tested for M-proteins and free light chains; those with a prior diagnosis of MGUS were excluded. Per protocol and informed consent, those who were found to have MGUS were randomized to 3 study arms: (1) Arm 1 (1164 participants) were not contacted, (2) Arm 2 (1159 participants) were followed based on current guidelines, and (3) Arm 3 (1164 participants) are to be given intensive diagnostic and monitoring. Those who progress will receive early treatment.

Of the participants screened, 3725 (4.9%) were found to have MGUS. The condition was more likely to be seen as participants grew older: 2.3% in the 40-59 age group, 6.2% in the 60-29 age group, and 12.9% in the 80-103 age group. MGUS prevalence was higher in males 5.9% vs 4.1%. Most participants were low-risk (38%) or low-to-intermediate risk (36%); 26% had high-intermediate risk, and high risk MGUS was seen in only 0.2% of cases (9 participants).

After median follow-up of 3 years, 194 patients had been diagnosed with LP: 9 in Arm 1, 92 in Arm 2, and 133 in Arm 3 (P < .001). Those in Arm 1 were diagnosed with smoldering Waldenström’s macroglobulinemia (SWM) (2), WM (2), chronic lymphocytic leukemia (CLL) (1) and MM (4).

Those in Arm 2 were diagnosed with amyloidosis (1), SWM (18), WM (2), CLL (2), non-Hodgkin lymphoma (NHL) (1), smoldering MM (56), and MM (12). Those in Arm 3 were diagnosed with amyloidosis (2), SWM (22), CLL (5), NHL (6), SMM (82), MM (16).

In a separate abstract, the investigators found that they “did not find MGUS to be associciated with SARS-CoV-2 susceptibility or COVID-19 severity. This is contrary to MM, which is preceded by MGUS.” The findings, they wrote, suggest that the immunosuppression in MGUS is different from that in MM, which has important implications for management and treatment.³

References

1. 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. Presented at: 63rd American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA, and virtual. Abstract 156. https://ash.confex.com/ash/2021/webprogram/Paper152333.html
2. iStopMM. International Myeloma Foundation. June 21, 2021. Accessed December 18, 2021. https://www.myeloma.org/black-swan-research-initiative/istopmm
3. Monoclonal gammopathy of undeterminded significance and COVID-19: results from the population-based Iceland Screens, Treats, or Prevents Multiple Myeloma Study (iStopMM). Presented at: 63rd American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Abstract 154. https://ash.confex.com/ash/2021/webprogram/Paper153145.html