We are international

Black Swan Research Initiative Researchers Speak Out and Publish

As the Black Swan Research Initiative (BSRI-- the IMF's innovative approach to finding a cure for myeloma --moves forward since its official launch in March, more and more myeloma researchers are contributing to the framework that is necessary to reach the project's key objectives. In recent weeks, two articles have appeared in medical journals supporting the underpinnings of the BSRI--in particular, the need to start curative therapy early in the disease to maximize chances of success, and secondly, the need to carefully monitor both the amount and the type of any residual disease that might persist after therapy.

In the journal Blood, Dr. Ola Landgren summarizes the strategy of  "pursuing the curative blueprint for early myeloma."  He both identifies the steps forward, as well as illustrating unanswered questions which will form the basis for sequential BSRI projects.

In Leukemia, the Salamanca University-led group reports on the use of multi-parameter flow cytometry immune phenotyping.  This flow technique to study the bone marrow is used in a variety of ways, including assessment of minimal residual disease (MRD).  In this case, the group reports the identification of patients with features of MGUS: a subgroup with a better outlook and the potential for long-term disease control, even in the presence of residual disease.  Here, the MRD has an "MGUS-like signature" and persists at a stable level for years without need for active therapy.  This illustrates the need for the multi-pronged approach of BSRI to identify the many ways to achieve best outcomes including cure.

Recap of Black Swan Research Initiative

To recap for those of you who may be unfamiliar with the BSRI, until recently the myeloma research community focused its efforts on comparing one treatment to another. Studies were conducted to determine which myeloma treatments or combinations of treatments resulted in comparatively better overall survival. We weren't confident about finding a cure--we were just looking to improve outcomes in myeloma patients by degrees. 

But in recent years, with the arrival of the novel myeloma therapies, it was realized that we are getting closer and closer to eliminating the disease entirely. A few of us began to think: Why not look at myeloma from a new perspective and come up with a plan to cure it?

That question was put before a small group of myeloma researchers at a brainstorming meeting held in Amsterdam in June 2012. There, the seeds of the Black Swan Research Initiative were sown and the strategy mapped out: The team would develop reliable tests for measuring minimal residual disease (MRD) in myeloma patients, and with this testing as our guide, we would enhance myeloma therapy to come up with a cure. This testing would be standardized and validated such that researchers around the globe would all use the same approach.

Importantly, the BSRI's international researchers would test multiple treatment approaches simultaneously to see which ones were coming closest to eliminating the disease entirely.

What MRD tests are available, and how can they be improved?

The BSRI team will use three techniques for testing MRD in myeloma patients.  We anticipate that these tests will be affordable and widely available. They are flow cytometry,  DNA, and  PET/CT scanning. When flow, DNA, and PET/CT scans are all negative, this is MRD-Zero. The BSRI proposes MRD-Zero as a new definition of response beyond traditional IMWG CR (complete response).  

However, validation is a critical step. If testing is negative (MRD-Zero), does this really predict long survival free of myeloma and, ultimately, a cure? We anticipate confirming this hypothesis as an early step in the BSRI project.

Why is MRD-Zero an important new response endpoint?

Without MRD-Zero testing, one is really working in the dark. Has the treatment worked well enough?  Is there residual disease?  Is there possible cure?  The ability to test myeloma patients for MRD-Zero is critical in order to develop new and potentially curative therapies.  

And this is what the BSRI is all about: developing new curative therapies for myeloma. The BSRI is structured to use MRD-Zero testing in clinical trials designed to achieve a cure. 

Dr. Durie sincerely appreciates and reads all comments left here. However, he cannot answer specific medical questions and encourages readers to contact the trained IMF Hotline staff instead. Questions are answered with input from Dr. Durie and/or other scientific advisors and IMWG members as appropriate. To contact the IMF Hotline, call  800-452-CURE, toll-free in the US and Canada, or send an email to hotline@myeloma.org. Hotline hours are 9 am to 4 pm PST. Friday summer hours are 9 am to 3 pm PDT. Thank you.


Which institutions can test for MRD?

Are the specific flow cytometry and DNA tests you'll be using well defined standard lab procedures yet or are they undergoing development/refinement? You indicate they will be affordable and widely available. Will current health insurance policies (including Medicare)cover them yet, or is that a work in progress?

This is an excellent question ! Both types of test are available and reimbursed ---- but not yet for myeloma. The standardization ,automation and validation in myeloma will occur as part of the Black Swan Research Initiative in the coming months.It is very important to make sure these tests are truly meaningful.We must confirm that MRD Zero indeed indicates a high likelihood of long long complete remission --- CURE !!

My husband and I are monthly donors to IMF to support them in this critical research. This testing will enable slight disease to be targeted and removed before it can develop fully. This is exciting. Thank you for keeping us informed.


The 3 tests for MRDzero are FCM, DNA and PET/CT.

What is the DNA test called. What is the procedure? How does it work and what does the test show for when it indicates MRD zero.

How must all three tests concur for it to define MRDzero. i.e.

What does FCM show for MRD zero?
What does DNA show for MRD zero?
What does PET/CT show for MRDzero?

thanks for your time

The DNA test currently proposed is one I which DNA which is sequence specific to the monoclonal type of the myeloma is quantified ( detected and measured ).Validation of the use of this type of test is ongoing. The current IMWG and BSRI definition of MRD ZERO is that testing by flow Cytometry ,DNA testing and by PET/CT are all negative.

I'm not sure I understand was is meant by "DNA" test. Please explain.

The DNA test means a test detecting DNA specific to the myeloma in an individual patient. Right now the main test is one which identifies the DNA specific for the myeloma ( dominant ) mono clone reflected by the monoclonal protein. This requires identification of the monoclone in a bone marrow sample from the start of treatment ( or @ a major relapse ). One then searches @ the DNA level to see if any of the monoclone is left in for example a patient with CR by IMWG criteria. One has to be cautious in case there is more than clone and/or if the clone may have morphed over time. Implementation of this type of DNA MRD testing is going to require careful validation.
I hope this explanation helps !

Leave a comment

To subscribe to this blog, enter your email address below: