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In an interview with OncologyLive, Brian G.M. Durie, MD, provided details about the Black Swan initiative and how he expects the project to develop.
Brian G.M. Durie, MD
Chairman, International Myeloma Foundation, North Hollywood, CA
When patients respond well to treatment for multiple myeloma, doctors can’t tell them whether they’ve been cured. That news comes 10 years later, after the patients have been monitored carefully for recurrence.
“During that time, you’re constantly watching and waiting for the second shoe to drop,” according to Brian G.M. Durie, MD, chairman and co-founder of the International Myeloma Foundation (IMF).
Through an IMF project, Durie and his colleagues are seeking to remove that long period of uncertainty for such patients. Under the Black Swan Research Initiative, the team plans to develop the first definitive criteria for a myeloma cure, and to set forth treatment plans to achieve those criteria.
The project will involve developing tests sensitive enough to determine whether patients have any myeloma cells left in their bodies following treatment. Those who don’t have such cells would be considered cured, and would know that in the short term. Those who do would be offered different treatments until tests show that their residual cancer cells have been eliminated.
Durie expects the work to be completed within three years.
“We’re ready to bridge the gap from long-term remission to cure, by identifying the best treatments at the best time to achieve the best objective, our objective being a new definition of cure based on a complete eradication of any residual myeloma,” Durie said.
In an interview with OncologyLive, Durie provided details about the Black Swan initiative and how he expects the project to develop.
Why is this project called Black Swan?
Here in the Northern Hemisphere, everybody knew swans were white until 1697, when Willem de Vlamingh sailed up Swan River in Western Australia and found black swans. Based on that, we realized swans could be any color. The idea is that we need to be open to new ideas, to look at things you may have been looking at already, but in a new light.
At the same time, we can learn something from the 2010 edition of The Black Swan: The Impact of the Highly Improbable, a guide to financial investment theory by Nassim Nicholas Taleb. The concept is that you invest 80% of your money in a standard fashion, but 20% in bold new ideas. The caveats are that: (1) you have to be willing to invest in a number of different projects in parallel, with the idea that one will be fruitful, and (2) you have to consider the best advice out there about which projects might pay off. Likewise, in trying to find a cure for myeloma, we need to look at different research projects in parallel and get the best advice possible to come up with likely projects.
Why is this the right time for the Black Swan Research Initiative?
With novel therapies, we see long-term complete remissions in 15% to 20% of our myeloma patients. These patients are getting to low levels of disease where they could have a minimal residual disease (MRD) level of zero. But we don’t have reliable, precise enough testing for MRD. The aim of this project is to come up with tests that are reliable and usable by groups around the world, and that are validated to confirm that they do, indeed, correlate with long-term remission and survival.
Who is conducting the Black Swan research?
A multinational consortium of leading myeloma experts. The consortium is a subset of the International Myeloma Working Group, the research arm of the IMF.
How will this group create tests that are sensitive enough to check for MRD zero?
There are two types of tests that we use on these patients now. One is automated flow cytometry, where you pass blood through a flow cytometer to see if there are any myeloma-like cells in the blood. The other is a test to see, at the molecular level, if there is any myeloma-related DNA in the blood.
With flow cytometry, we’re talking about making the test more sensitive and specific for myeloma. That will involve just a bit of tweaking. There are computer software programs that will need a new algorithm with a slightly different cocktail for folks with myeloma.
Once that is done, we’re very optimistic about getting the test into use, because this type of flow cytometry is widely used at centers across the country and world.
It will be possible to roll this out rather quickly and make it widely available for diagnosis without FDA approval, because it simply involves modifications of existing technology that has been approved for use in the US and most countries.
No new machines will be needed to conduct the updated versions of these tests.
What kind of timeline do you envision for this project?
We’re hopeful to have both the flow cytometry and molecular testing available in the next three to six months.
Then, in the following 2Â½ years, we will conduct validation of the tests, primarily within clinical trials and at no cost to patients. Part of our work will be to identify patients who have been in complete remission for 10 years, and evaluate them to see if they have achieved MRD zero. Then, we’ll be able to correlate the test to say, “This level of MRD does correlate with 10-year survival.”
After that, there will be meetings with the FDA, which will require validation information to approve MRD as an accepted endpoint. A primary goal of the Black Swan Research Initiative is to acquire and submit the necessary documentation as rapidly as possible–hopefully in 2014.
Once all that has been completed, the IMF anticipates releasing new guidelines for myeloma treatment with MRD as an endpoint.
In addition to eliminating uncertainty for patients, what outcomes do you anticipate as a result of this project?
We’ll have the confidence to treat more aggressively in the first six months to get to that MRD zero. We’ll front-load the therapy, and, if we achieve MRD zero, we’ll be able to stop treatment. There will be some patients in whom we also want to use maintenance therapy, but, in general, this is going to reduce the amount of treatment.
In addition, trials will be much faster. You could have an endpoint of MRD zero after six months, instead of a specified outcome after five to 10 years. This would dramatically shorten trials and reduce their cost.
Where is the funding for this project coming from?
The foundation has sought and been receiving private funding. In addition, we are seeking corporate sponsors. We would like to see pharmaceutical companies fund trials of their drugs that will test the ability of the agents to get patients to MRD zero.