Established in early 2016, the iStopMM® project to screen the entire population of Iceland for MGUS (monoclonal gammopathy of undetermined significance), the precursor to myeloma, will celebrate its two-year anniversary in November. The response to the IMF-supported study has been unprecedented: More than 80,000 Icelanders over the age of 40 have signed up and have been undergoing testing and monitoring, as I reported late last year.
Now, a new project will attempt to replicate iStopMM’s large, population-based approach in the U.S. Funded by Stand Up to Cancer (SU2C), an entertainment-industry-based charitable organization that raises money for cancer research, the project will attempt to recruit approximately 50,000 individuals over the age of 45. The target population for the survey includes people with first-degree relatives who have had multiple myeloma, and African-Americans, since African-Americans are three times more likely than whites to develop the precursor conditions and tend to develop them at an earlier age.
Challenges to success
Led by Dr. Irene Ghobrial (Dana-Farber Cancer Institute), the SU2C team also includes Dr. Joseph Mikhael (IMF’s Chief Medical Officer). It is fitting that the ongoing iStopMM Black Swan Research Initiative-supported project in Iceland will now be linked to a similar effort in the U.S.
“It is such an honor for me and the IMF to be a part of the SU2C Dream Team as we apply the Iceland strategy to African-Americans and relatives of our myeloma patients,” said Dr. Mikhael. “This is the only way to answer critical questions about the prevalence of myeloma and the best way to intervene.”
Such large, population-based studies are extremely challenging, and the U.S. effort can learn from the techniques used for successful recruitment in Iceland. These included a broad social media outreach campaign and endorsement by high-profile government leaders. Principal Investigator Dr. Sigurdur Kristinsson (University of Iceland) had some advantages in that all Icelanders have automatic health care, and, at routine check-ups, patients’ blood is drawn and can be made available for special testing.
In addition, Icelandic project participants already have full DNA sequencing results available, as well as family tree lineages extending back 200 years and more. So, the genetic make-up of individuals with MGUS and smoldering multiple myeloma (SMM) is available for research comparisons.
The SU2C team will also face what a recent study demonstrated is a relatively low rate of participation by African-Americans in health research studies. It will be important to communicate that the project offers a historic opportunity for African-American patients to have first access to state-of-the-art diagnostics, early interventions, and the possibility of a cure.
Early intervention is key
Like the IMF’s Black Swan Research Initiative, the SU2C project proposes that early identification of myeloma’s precursor conditions allows for potential early interventions. The treatments in Iceland, for example, are part of the series of myeloma “Cure Trials” taking place within the BSRI project in the U.S., Spain, and Iceland:
- The initial results with the CESAR trial (carfilzomib, lenalidomide, and dexamethasone, followed by autologous hematopoietic cell transplantation and consolidation therapy in high-risk smoldering myeloma) were reported by Dr. Maria-Victoria Mateos at ASH in 2017.
- The ASCENT trial (daratumumab, carfilzomib, lenalidomide, and dexamethasone in high-risk smoldering myeloma) is about to launch in the U.S.
- And the iStopMM treatment protocols (carfilzomib, lenalidomide, and dexamethasone in both active myeloma and SMM) are just beginning in Iceland.
This series of trials allows an initial assessment of the value of early intervention based upon the achievement of sustained MRD (minimal residual disease) negativity at the 10-to-the-negative-6th level at one-year, three years, and five years. This means that at one year, three years, and five years post-therapy, patients are tested for the presence of even one myeloma cell found among one million bone marrow cells, and have PET scans to check for any myeloma that may be growing outside the bone marrow. In the CESAR trial, it is very encouraging that the initial level of MRD negativity is 62 percent, giving hope that some patients will indeed be cured because of early screening and early intervention.
Clearly, by one definition, it will take time to know the true success of the Cure trials. For patients, “living to old age and dying from something else” is that definition. We are hoping for this as we build on early promising results.
The SU2C project is an important new effort to follow on this path. The challenges in the U.S. healthcare system are serious hurdles to overcome. I hope that lessons learned from the iStopMM project can accelerate the SU2C team’s success in screening, and inspire further testing studies and potential early interventions in the U.S.
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