Is MRD testing ready for “prime time”?
July 14, 2016
Is MRD testing ready for “prime time”?WRITTEN BY: Brian GM Durie MD
The answer is a definite yes and no! Yes, it is now a priority to test for minimal residual disease (MRD) in myeloma clinical trials. However, no, MRD testing is not yet recommended in routine clinical practice. But I’m pleased to report that we are getting there.
In the next two weeks, the new response criteria from the International Myeloma Working Group® incorporating MRD testing will be published in The Lancet Oncology. Achieving consensus by more than 200 of the world’s top myeloma researchers on these criteria marks a significant accomplishment, two years in the making, by lead author Dr. Shaji Kumar of Mayo Clinic and his IMWG colleagues.
MRD testing in the Black Swan Research Initiative
The publication of the new response criteria also represents an important step forward for the IMF’s mission to find a cure. As you may know, MRD testing has been a crucial element of our Black Swan Research Initiative® since its inception in 2012. We have been pleased to see that in the four years since then, MRD testing in myeloma has been embraced by the rest of the myeloma research community. But with the publication of the new response criteria, MRD testing has now taken its place as the gold standard of disease measurement—much as we envisioned—and one which now allows us to determine exactly where a patient stands in the course of the disease and how effective treatment has been.
What, exactly, is MRD negative, MRD positive?
In the new IMWG MRD response criteria, exact definitions are spelled out for what constitutes a patient considered to be “MRD negative”: at what level and with which tests. Either Next-Generation Sequencing (NGS) or Next-Generation Flow (NGF) can be used, with a cutoff which has to be at least less than 1 in 100,000 cells, but hopefully less than 1 in a million cells. There are two additional categories in the new response criteria to measure MRD: one in which PET/CT scanning is also negative and a “sustaining MRD negative” category in which the MRD negative testing remains negative after 1 year – a key endpoint.
Having “sustained MRD negative” as an endpoint in clinical trials provides an incredibly important yardstick to point the way to the achievement of cure—which is defined as an MRD negative level sustained at 3 years and 5 years. It is wonderful to have this framework for clinical trial design.
MRD testing in the clinic
But what about MRD testing in the clinic? I very much appreciate and understand the patient perspective that “confirming MRD negative status” would be very reassuring. And I know from talking to patients they are rightfully anxious to take this next step. However, I have to point out a couple of challenges in the short term.
1. Right now, “routine” MRD testing is not fully set-up and standardized. Nor is there an accepted reimbursement plan. The fact that a sample can be sent to one laboratory and get one answer (let’s say “negative”) and another lab with a different answer (let’s say “positive”) is very disturbing. This issue needs to get sorted out before routine testing is recommended. We hope that standardization and quality controls for NGF will be in place for a significant number of laboratories in the US within 6 to 9 months, and, the Black Swan research team has been working nonstop to make that happen.
2. It is additionally important to be aware of the second challenge. We need to fully understand the significance of “MRD negative” and “MRD positive” test results. If, for example, a patient is on maintenance therapy, doing well, and is “MRD negative,” is it safe to stop maintenance or maybe continue for a further six months or longer? We don’t know. If such a patient has an “MRD positive” test result, what does that mean? Should maintenance be changed or is everything actually just fine in terms of achieving ongoing benefit with the same maintenance? These are very important questions, which along with many others, need to be answered in top priority clinical trials.
So there you have it: A snapshot of the status of MRD testing. I know there are many more questions about MRD, and I have only really scratched the surface with this summary. I invite you to send in your questions so that we can enrich this discussion and set the stage for future developments. Stay tuned!
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