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.
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