WHAT IS THE BSRI™?
The Black Swan Research Initiative™ is the IMF’s new research platform designed to find a cure for myeloma. It is based on:
- the latest scientific understanding of how myeloma develops in the body
- the most technologically advanced methods to measure and quantify disease development in the body
- the ability to measure and quantify the response to treatments
As we further develop these capabilities we can assess the best treatments to use, the best time to use them and eventually determine which patients will respond best to which treatments.
HOW WILL THE BSRI ASSESS A CURE?
One arm of the BSRI will perfect sensitive tests to track the myeloma cells in the body. These tests exist – it is just a matter of “fine tuning” them to myeloma. After treatment we know patients are left with Minimal Residual Disease. Our goal is to use treatments to reach a minimal level of this residual disease, or MRD, and when we reach no residual disease, MRD-Zero™, we believe we have a cure. And we’ll test further.
One advantage to this approach is that we expect to be able to assess the efficacy of a treatment quickly and measurably, in months instead of years. This is possible because the measurement will be objective, instead of a comparison to an earlier treatment.
WHAT MAKES YOU THINK THIS WILL WORK?
The approach is based on new scientific understandings, but they are solid, well-documented scientific understandings.
We know that myeloma differs genetically between patients. We now also know myeloma differs genetically within a patient over time. When we treat myeloma, we are treating the dominant genetic variation that we call a clone. As the therapies work on this clone, other clones grow in the background and take hold - remission ends and the emerging genetic variation may be more difficult to treat. We understand this and we see it happening. BSRI trials, along with our enhanced monitoring and molecular testing leading to proposed treatments, are based on this new, deeper understanding of myeloma at the molecular level.
Without this type of molecular testing for myeloma, you can’t document if you have a molecular remission or not, and you’re not able to assess how good the treatment is. So with very, very sensitive molecular testing, and the most advanced treatments, we’re proposing we will get to a point of true eradication of the myeloma.
In addition, we have a few patients we believe have already been cured, so this is not just theory. Now we are taking a closer look at them to better understand how and why they were cured, so we can apply these findings to more patients.
HOW LONG WILL THIS TAKE?
We expect to begin clinical trials within the year and could have the first answers within three years. Initially we believe we can CURE 20% of myeloma patients (150,000 people), and then expand the circle to include more and more patients as we gain understanding of the disease, treatments and MRD-Zero.
Remember, even patients who are not initially cured will be helped with a more exact measurement of their disease and better applications of current treatments. So in addition to finding a cure, we will expand the group of patients living well with their disease
WHICH PATIENTS WILL BE ELIGIBLE TO PARTICIPATE IN THE BSRI?
The goal of the BSRI is to help all patients, so we are beginning by expanding the test population to include patients who are not traditionally treated. These are the patients with early disease. They are often not treated because their myeloma may be dormant for a decade or more. But what if we could wipe out the myeloma before it becomes fully “active”? We will assess these patients to determine who is at risk of converting to active disease and then assess if they can benefit from treatment, and even reach a cure.
Remember, what we learn from each patient group can and will be applied to all other patients as we learn who responds best to which treatments and why.
Even when we don’t achieve a cure, we will change the course of the disease and treatment, asking and answering the following questions:
- How can we minimize residual disease?
- When MRD is reached, can we stop treating?
- How many of the patients who have been in complete remission (CR) for 10 years or more are actually at MRD-Zero?
HOW IS THIS DIFFERENT THAN CLINICAL TRIALS OF EXISTING DRUGS NOW?
We are recruiting and assigning patients by molecular characteristics of their disease. We are measuring the impact of treatment using objective, measureable changes in the quantity of disease cells, not observations of markers and symptoms. Using these methods we expect to have results much sooner than clinical trials with traditional “end-points,” such as progression-free survival (PFS). We want to move beyond just impacting the disease—although that remains an important goal—to eliminating the disease.
WHAT ROLE WILL CLINICAL TRIALS PLAY IN THE BSRI?
Clinical trials are being designed to assess the validity of MDR as an end point. The treatment within these trials will vary and may not be appropriate for an individual patient. Key analyses will occur within trials that have already been completed, and from which 5 to 10 years of follow-up can already be assessed.
HOW DO I JOIN A CLINICAL TRIAL FOR THE BSRI? IS THERE A WAITING LIST?
New trials are being designed to assess the validity of Minimum Residual Disease as an end point. There are not and will not be waiting lists for trials. We may seek patients who may benefit from a particular therapy.
CAN YOU TELL ME ABOUT THE AVAILABILITY OF MRD TESTING AND THE POSSIBLE INSURANCE COVERAGE FOR SUCH TESTING?
Initially, MRD testing will be done for free within trials. Data from these trials are needed first. After that, the tests will be commercially available, and the plan is for the tests to be both affordable and reimbursed.
WHAT IMPACT WILL THIS NEW MOLECULAR TESTING FOR MYELOMA HAVE ON THE TESTS ON WHICH WE CURRENTLY USE? WILL ANY OF THEM BE RENDERED OBSOLETE?
As blood testing for flow and molecular become key, it is possible, even likely, that some of our standard testing will become obsolete. But this transition will occur over time. Unfortunately, physicians’ habits change slowly (for example, some still rely on X-rays when other imaging is really needed). HevyLite may replace serum protein electrophoresis (SPEP) + immunofixation electrophoresis (IFE). FreeLite will continue. New types of PET/ CT scans will also become more important. FISH testing will become obsolete as more reliable molecular testing becomes available.
All of this will be better for patients.
WILL I STILL NEED A BONE MARROW BIOPSY?
Fortunately, the reliance on follow-up bone marrow will lessen, which is good.
HOW MUCH WILL BSRI COST?
Over time, we expect to raise approximately $15 to $20 million for a program of this magnitude. In addition to initiating research, we are actively fund raising. If you are interested in supporting the BSRI – please contact IMF Vice President of Development, Heather Cooper Ortner.
WHO IS IN THE BSRI?
The BSRI is made up of some of the top myeloma researchers in the world. Dr. Brian Durie and Dr. Ola Landgren are two of the members of this elite research team. Some of the research is proprietary and some requires additional funding, so the full project will be rolled out in stages as appropriate
IF BSRI USES CURRENT TREATMENTS, WHY AREN’T PATIENTS BEING CURED NOW?
Some are being cured. We just don’t have the technology in place to detect and confirm all of the cures. We also know a cure is more than “just” the right treatments. One of the BSRI projects will be to develop clinical trials to find out which combination provides the best outcome for each type of myeloma. It involves applying the right combination of treatments applied to the right patients at the right time. By categorizing patients by the molecular characteristics of their disease we can better apply these treatments to achieve MRD and then MRD-Zero.
WHAT’S THE LINK BETWEEN THE IMF’S BANK ON A CURE® AND THE BSRI?
Launched in 2005, the IMF’s Bank On A Cure®—the first global myeloma-specific DNA bank and research initiative—has resulted in a vast bank of genetic information to help us assess differences in DNA between individuals, and how those differences affect an individual’s susceptibility to develop myeloma, as well as how the body handles different types of drugs. In other words, Bank on a Cure examines the DNA of individuals. The BSRI will look at the DNA of myeloma.
WHAT IS THE DIFFERENCE BETWEEN YOUR RESEARCH AND WHAT OTHER BLOOD CANCER ORGANIZATIONS ARE DOING?
It is not our place to comment on other projects, except to say that finding a cure is a goal— not a competition.
What we can say about our project is that it is based on a new application of science at the molecular level. Our multi-pronged research project is based on the growing understanding of how myeloma develops in the body, the growing ability to assess, measure and quantify the disease development in the body, and to measure and quantify the response to treatments. We also have the experts in place around the world, and much of this work is already underway. We are excited and encouraged by our initial progress.
WHY “BLACK SWAN”?
Our approach is beyond thinking outside the box. It is to take an approach so unique and so imaginative that we don’t even see the box. It is like the black swans that Europeans couldn’t even image because they had never seen one. Then, in 1697, Willem de Vlamingh sailed up Swan River in Western Australia and found black swans, and people were amazed. We believe our own Black Swan Research Initiative will also amaze with positive, life-changing results.