The iStopMM (Screens, Treat, or Prevent Multiple Myeloma) project was launched on November 15, 2016, with strong support from the Black Swan Research Initiative®. Two weeks ago, IMF President & CEO Susie Durie, Senior Vice President of Clinical Education & Research Initiatives Lisa Paik, and I visited the University of Iceland to celebrate the one-year anniversary with Principal Investigator Dr. Sigurdur Kristinsson and his 16-member iStopMM team. I am thrilled to report that the results to date are beyond everyone’s expectations.
There has been an unprecedented response to the study from the Icelandic people. Of approximately 140,000 individuals over 40 years of age who were asked to participate and be screened for possible MGUS, SMM or active MM, thus far 77,777 have signed up, agreeing to be tested as well as randomized to be more rigorously tested and/or possibly treated with interventional myeloma therapy.
Largest study of its kind
This is already the largest myeloma-related study requiring patient participation ever conducted. More than 35,000 blood samples are available for testing at this point, with between 40,000 and 50,000 more to come! This is an enormous onslaught of samples for the The Binding Site (TBS) testing laboratory in Birmingham, UK, according to Kelly Endean, Head of Medical Science Liaison. Even with TBS's 100 percent commitment to the iStopMM project (testing approximately 300 samples/work day), the required testing to confirm presence or absence of a monoclonal protein will require many months to complete.
As the results poured in to the iStopMM clinic in Reykjavik, it was gratifying to see that laboratories and biobank are all up and running. Every day, between 7 and 10 participants come in to the clinical center to complete questionnaires, receive education about MGUS or SMM, get an ECG test, provide blood and urine samples, share basic medical history, and have a physical examination, bone marrow biopsy, X-ray, and CT scans. Again, this is a huge undertaking by three nurses (Gudrun Asta, Sara Lovisa, and Ingibjorg Hrefna) and a laboratory assistant (Sigurlina). In addition, the nurses travel by plane monthly to three remote centers in Iceland: Akureyri, Isafjordur, and Egilsstadir.
Meeting with each participant (and typically several family members) to explain the study in person and conduct the baseline evaluation and testing is both very rewarding and extremely time-consuming. This personal and individual commitment to achieve active participation is truly remarkable, as the IMF team witnessed on our visit to the clinical center.
A research treasure trove
The IMF team also visited the biobank facilities within the DeCode building complex. The huge (30-plus-foot-long) and sophisticated biobank is a one-of-a-kind facility. Using robotics, small samples (aliquots) of stored blood, bone marrow, and/or separated DNA can be individually accessed using a secure, privacy-protected barcoding system. This allows precise selection of required samples without unfreezing or damaging the main biobank-stored samples. Watching the robotic system swing into action and deliver the tiny barcoded sample to the requesting researcher is a science fiction-like experience. Stored safely in Iceland's biobank, samples from the iStopMM program represent a treasure trove for researchers both now and for many years to come.
Diverse and expanding research opportunities
The project’s core team has expanded to include additional office personnel, flow cytometry laboratory technicians, and collaborators at the University of Iceland's Departments of Radiology, Hematology and Hematopathology, Psychology, Cardiology, Nephrology, Neurology, and Hepatology.
This expansion of the iStopMM team reflects the tremendous promise and scope of research opportunities that are emerging, thanks to iSTOPMM's huge early enrollment. Nurses and research experts are being successfully recruited to come to, or return to, Iceland to join the project. The ambitious goals of the core team under the leadership of Dr. Kristinsson are becoming infectious!
MRD monitoring by flow cytometry
A very important project supported by Black Swan Research funding is the flow cytometry laboratory, which began with the arrival of the new Becton Dickinson flow cytometer on May 4th, 2017. Since then, over 120 samples have been processed from 63 participants. Full set-up and validation have been achieved in coordination with Dr. Bruno Paiva and the flow team at the University of Salamanca in Spain. The levels of myeloma cells in both bone marrow and blood are being assessed, and early indications are that blood monitoring will be a very helpful tool in the early and prognostic evaluation of both MGUS and SMM. The intent is to conduct both MRD monitoring and serial immune profiling.
Expectations for 2018
So, what will be the iStopMM project’s accomplishments moving into 2018?
The pattern of features associated with the newly discovered monoclonal proteins will start to take shape. Rather surprisingly, results from the early testing are falling into two distinct groups. One group is made up of patients with very low levels of monoclonal protein, who have very low-risk or early MGUS with a low likelihood of progression to SMM or MM. The second group consists of patients with higher levels of monoclonal protein, who are primarily at “pre-myeloma” stage with intermediate or high-risk SMM. There is a lack of higher-risk MGUS or lower-risk SMM. If this trend holds up from this “screening population,” clear management guidelines may be much simpler than expected for the earlier and later disease groups.
As patients proceed with baseline evaluation, the need for early intervention will become apparent. In the iStopMM program, as in the CESAR “Cure” trial and the soon-to-open ASCENT “Cure” trial, patients will be offered KRd as a decisive early intervention.
An innovative new study led by Sæmundur Rögnvaldsson will assess neuropathy in patients with MGUS. This potentially debilitating complication is very important, even in the absence of progression of the underlying MGUS. Careful studies will lead to better therapies and outcomes for affected patients.
Among the many other exciting opportunities, the potential studies of genetics here are tantalizing. Because patients have had DNA sequencing performed, it will be possible to identify key mutations linked to the development of MGUS and to progression of SMM to myeloma.
So many ideas and opportunities! There will be many updates moving forward. Stay tuned!
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