The IMF’s signature Black Swan Research Initiative® (BSRI®) is forging ahead at full speed in early 2017, with many accomplishments behind us and many more exciting projects under way. We share with you the current BSRI checklist and a preview of the exciting projects that will unfold this year.
The BSRI team has defined and overcome the first obstacle to finding a cure for myeloma by developing a very sensitive, reliable, standardized, and affordable test to quantify and characterize any myeloma cells that may remain after a patient is in complete response (CR). The new test, known as Next-Generation Flow (NGF), is a flow cytometry technique plus a specialized software package that were developed by researchers in Spain to detect even a single myeloma cell surviving among one million bone marrow cells.
Last October, 120 researchers from myeloma laboratories around the globe gathered in Salamanca, Spain, for intensive training in NGF. Researchers from 60 labs in 26 countries worldwide attended the training workshop in addition to attendees from 12 sites in the US. The BSRI’s MRD Consortium represents centers in North and South America, Africa, Asia, Australia, and Europe. Three of the labs in the US – Mayo Clinic (Rochester, MN), Roswell Park Cancer Center (Buffalo, NY), and the SWOG Lab at the Levine Cancer Center (Charlotte, NC) – are reference labs to which patient bone marrow samples can be sent for MRD testing from any other hospital, clinic, or doctor’s office.
On March 10, 2017, the journal Leukemia published an article by members of the BSRI team on the design and validation of NGF.
The Icelandic project known as Iceland Screens, Treats, Or Prevents Multiple Myeloma (iStopMM®) launched officially in November 2016. In just four months since it opened, iStopMM has enrolled more than 70,000 participants! Its aim is to screen approximately 120,000 residents of Iceland who are over 40 years of age for evidence of MGUS, SMM, or myeloma. Researchers, under the direction of principal investigator Dr. Sigurdur Kristinsson, calculate that approximately 4% of those screened will have MGUS, which will add up to over 4,000 MGUS patients with full accrual. This is the largest population-based screening study for myeloma and its earlier disease precursors that has ever been attempted.
Iceland, with its small and networked population and centralized healthcare system, is the ideal place to conduct such a study. Not only will this project allow researchers to observe patterns of occurrence, but they will be able to follow subjects with early disease to see how it progresses. Moreover, monitoring patients with MGUS for many years will demonstrate which prognostic tests are most reliable as indicators of disease progression. We will also learn which patients benefit most from early intervention, as those identified with high-risk smoldering myeloma will be invited to participate in a treatment trial.
Because much of the Icelandic population has already undergone genetic coding, iStopMM researchers will be able to use this genetic data to look for linkages to particular family gene patterns in those with MGUS. The chances are excellent that answers will be found to help the BSRI team understand the biology of why people develop MGUS and how it can be prevented.
The ASCENT trial
The ASCENT trial, headed by Dr. Shaji Kumar of the Mayo Clinic (Rochester, MN), will use a combination of carfilzomib + lenalidomide + dexamethasone + daratumumab with/without stem cell transplant in an attempt to cure patients with high-risk smoldering multiple myeloma (SMM). This trial is scheduled to open in the coming months at the 12 MRD Consortium sites in the US.
Other clinical trials
Multiple clinical trials are being set up in the US, Europe, and the Asia-Pacific region to study and treat patients with MRD-positive disease. These studies will use new therapies to attempt to eliminate resistant MRD myeloma cells. In addition, there are more than 30 BSRI projects under way around the globe to study various aspects of residual disease. There is also an ongoing study of long survivors to better characterize and understand the nature of their disease, treatments, and response to treatment.
The research conducted by BSRI investigators over the course of the past three years is resulting in tangible benefits for patients. With accurate and accessible MRD testing, we have an endpoint to assess deep response; we have clinical trials to attempt to cure early disease; we have a screening trial to understand the causes and biology of precursor disease and to prevent its progression; and we will soon have trials to eradicate MRD.